bluuebunny/crossref_metadata_2025 huggingface dataset:
Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns
Authors: Meulemans Daniel , Bronner-Fraser Marianne
Published: April 2021

The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However,migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.
MEC-8 regulates alternative splicing ofunc-52transcripts inC. eleganshypodermal cells
Authors: Spike Caroline A. , Davies Andrew G. , Shaw Jocelyn E. , Herman Robert K.
Published: April 2021

Previous work has shown that C. elegans MEC-8 is a putative RNA-binding protein that promotes specific alternative splices ofunc-52 transcripts. unc-52 encodes homologs of mammalian perlecan that are located extracellularly between muscle and hypodermis and are essential for muscle development in both embryos and larvae. We show that MEC-8 is a nuclear protein found in hypodermis at most stages of development and not in most late embryonic or larval body-wall muscle. We have also found that overexpression of MEC-8 in hypodermis but not muscle can suppress certainunc-52 mutant phenotypes. These are unexpected results because it has been proposed that UNC-52 is produced exclusively by muscle. We have constructed various tissue-specific unc-52 minigenes fused to a gene for green fluorescent protein that have allowed us to monitor tissue-specificmec-8-dependent alternative splicing; we show that mec-8must be expressed in the same cell type as the unc-52 minigene in order to regulate its expression, supporting the view that MEC-8 acts directly on unc-52 transcripts and that UNC-52 must be synthesized primarily by the hypodermis. Indeed, our analysis of unc-52 genetic mosaics has shown that the focus of unc-52 action is not in body-wall muscle but most likely is in hypodermis.
The Hox geneabdominal-Aspecifies heart cell fate in theDrosophiladorsal vessel
Authors: Lovato TyAnna L. , Nguyen Thiennga P. , Molina Marco R. , Cripps Richard M.
Published: April 2021

The Drosophila melanogaster dorsal vessel is a linear organ that pumps blood through the body. Blood enters the dorsal vessel in a posterior chamber termed the heart, and is pumped in an anterior direction through a region of the dorsal vessel termed the aorta. Although the genes that specify dorsal vessel cell fate are well understood, there is still much to be learned concerning how cell fate in this linear tube is determined in an anteroposterior manner, either in Drosophila or in any other animal. We demonstrate that the formation of a morphologically and molecularly distinct heart depends crucially upon the homeotic segmentation geneabdominal-A (abd-A). abd-A expression in the dorsal vessel was detected only in the heart, and overexpression of abd-Ainduced heart fate in the aorta in a cell-autonomous manner. Mutation ofabd-A resulted in a loss of heart-specific markers. We also demonstrate that abd-A and sevenup co-expression in cardial cells defined the location of ostia, or inflow tracts. Other genes of theBithorax Complex do not appear to participate in heart specification,although high level expression of Ultrabithorax is capable of inducing a partial heart fate in the aorta. These findings for the first time demonstrate a specific involvement for Hox genes in patterning the muscular circulatory system, and suggest a mechanism of broad relevance for animal heart patterning.
Pax6is required for the normal development of the forebrain axonal connections
Authors: Jones Lucy , López-Bendito Guillermina , Gruss Peter , Stoykova Anastassia , Molnár Zoltán
Published: April 2021

The transcription factor PAX6 has been implicated in forebrain patterning,cerebral cortical arealization and in development of thalamocortical connections. Using a Pax6/lacZ knockout mouse, in which the endogenous Pax6 expression is reflected by β-galactosidase activity, we have studied the consequences of the loss of Pax6function on thalamocortical (TCA) and corticofugal axon (CFA) pathfinding during the period of embryonic day (E) 14.5 to E18.5. Carbocyanine dye tracing in Pax6 heterozygotes (Pax6+/-) and Pax6wild-type (Pax6+/+) brains revealed that CFAs and TCAs temporarily arrested their growth at E14.5 at the border of theβ-galactosidase-positive region at the pallial/subpallial boundary(PSPB), before they continued towards their targets. However, in Pax6homozygous (Pax6-/-) embryos, CFAs and TCAs were unable to encounter each other at the PSPB and reach their final targets. Instead of crossing the PSPB, they had the tendency to descend into the ventral pallium in large aberrant fascicles. In addition, cells with a presumptive guide-post function, which are normally situated in the ventral thalamus, internal capsule and hypothalamus, were more dispersed in the hypothalamus and ventral pallium. These pathfinding defects were confirmed by immunohistochemistry for L1 and TAG1, markers of the early axonal connections. The aberrant development of axonal connections in absence of Pax6 function appear to be related to ultrastructural defects of cells along the PSPB, as well as to a failure of axonal guidance molecule expression, including Sema3c and Sema5a.
The limb identity geneTbx5promotes limb initiation by interacting withWnt2bandFgf10
Authors: Ng Jennifer K. , Kawakami Yasuhiko , Büscher Dirk , Raya Ángel , Itoh Tohru , Koth Christopher M. , Esteban Concepción Rodríguez , Rodríguez-León Joaquín , Garrity Deborah M. , Fishman Mark C. , Belmonte Juan Carlos Izpisúa
Published: April 2021

A major gap in our knowledge of development is how the growth and identity of tissues and organs are linked during embryogenesis. The vertebrate limb is one of the best models to study these processes. Combining mutant analyses with gain- and loss-of-function approaches in zebrafish and chick embryos, we show that Tbx5, in addition to its role governing forelimb identity,is both necessary and sufficient for limb outgrowth. We find thatTbx5 functions downstream of WNT signaling to regulateFgf10, which, in turn, maintains Tbx5 expression during limb outgrowth. Furthermore, our results indicate that Tbx5 andWnt2b function together to initiate and specify forelimb outgrowth and identity. The molecular interactions governed by members of the T-box,Wnt and Fgf gene families uncovered in this study provide a framework for understanding not only limb development, but how outgrowth and identity of other tissues and organs of the embryo may be regulated.
growth arrest specific gene 1acts as a region-specific mediator of theFgf10/Fgf8regulatory loop in the limb
Authors: Liu Ying , Liu Chunqiao , Yamada Yoshihiko , Fan Chen-Ming
Published: April 2021

Proximal-to-distal growth of the embryonic limbs requires Fgf10 in the mesenchyme to activate Fgf8 in the apical ectodermal ridge (AER),which in turn promotes mesenchymal outgrowth. We show here that the growth arrest specific gene 1 (Gas1) is required in the mesenchyme for the normal regulation of Fgf10/Fgf8. Gas1 mutant limbs have defects in the proliferation of the AER and the mesenchyme and develop with small autopods, missing phalanges and anterior digit syndactyly. At the molecular level, Fgf10 expression at the distal tip mesenchyme immediately underneath the AER is preferentially affected in the mutant limb, coinciding with the loss of Fgf8 expression in the AER. To test whether FGF10 deficiency is an underlying cause of the Gas1 mutant phenotype, we employed a limb culture system in conjunction with microinjection of recombinant proteins. In this system, FGF10 but not FGF8 protein injected into the mutant distal tip mesenchyme restores Fgf8 expression in the AER. Our data provide evidence that Gas1 acts to maintain high levels of FGF10 at the tip mesenchyme and support the proposal that Fgf10expression in this region is crucial for maintaining Fgf8 expression in the AER.
A new role for Mos inXenopusoocyte maturation: targeting Myt1 independently of MAPK
Authors: Peter Marion , Labbé Jean-Claude , Dorée Marcel , Mandart Elisabeth
Published: April 2021

The resumption of meiosis in Xenopus arrested oocytes is triggered by progesterone, which leads to polyadenylation and translation of Mos mRNA, then activation of MAPK pathway. While Mos protein kinase has been reported to be essential for re-entry into meiosis in Xenopus, arrested oocytes can undergo germinal vesicle breakdown (GVBD) independently of MAPK activation, leading us to question what the Mos target might be if Mos is still required. We now demonstrate that Mos is indeed necessary, although is independent of the MAPK cascade, for conversion of inactive pre-MPF into active MPF. We have found that Myt1 is likely to be the Mos target in this process, as Mos interacts with Myt1 in oocyte extracts and Mos triggers Myt1 phosphorylation on some sites in vivo, even in the absence of MAPK activation. We propose that Mos is involved, not only in the MAPK cascade pathway, but also in a mechanism that directly activates MPF in Xenopus oocytes.
Organ-specific cell division abnormalities caused by mutation in a general cell cycle regulator inC. elegans
Authors: Kostić Ivana , Roy Richard
Published: April 2021

The precise control of cell division during development is pivotal for morphogenesis and the correct formation of tissues and organs. One important gene family involved in such control is the p21/p27/p57 class of negative cell cycle regulators. Loss of function of the C. elegans p27 homolog, cki-1, causes extra cell divisions in numerous tissues including the hypodermis, the vulva, and the intestine. We have sought to better understand how cell divisions are controlled upstream or in parallel to cki-1 in specific organs during C. elegans development. By taking advantage of the invariant cell lineage of C. elegans, we used an intestinal-specific GFP reporter in a screen to identify mutants that undergo cell division abnormalities in the intestinal lineage. We have isolated a mutant with twice the wild-type complement of intestinal cells, all of which arise during mid-embryogenesis. This mutant, called rr31, is a fully dominant, maternal-effect, gain-of-function mutation in the cdc-25.1 cell cycle phosphatase that sensitizes the intestinal lineage to an extra cell division. We showed that cdc-25.1 acts at the G1/S transition, as ectopic expression of CDC-25.1 caused entry into S phase in intestinal cells. In addition, we showed that the cdc-25.1(gf) requires cyclin E. The extra cell division defect was shown to be restricted to the E lineage and the E fate is necessary and sufficient to sensitize cells to this mutation.
A changing morphogen gradient is interpreted by continuous transduction flow
Authors: Bourillot P.-Y. , Garrett N. , Gurdon J. B.
Published: April 2021

In vertebrate development, most signalling factors behave as morphogens, eliciting divergent cell fates according to their concentration. We ask how cells interpret morphogen concentration as it changes during the establishment of a gradient. Using dissociated blastula cells of Xenopus exposed to activin for only 10 minutes, we have followed the phosphorylation of tagged Smad2, the principal activin transducer, from a cytoplasmic pool to the nucleus in real time. We show that a changing concentration of extracellular activin is rapidly and continuously transduced to provide a corresponding nuclear concentration of Smad2, even though gene response may be delayed for several hours. Nuclear Smad2 concentration changes up as the extracellular concentration of activin increases. We conclude that cells interpret a changing extracellular concentration by maintaining a continuous flow of activated transducer from a large cytoplasmic pool to the nucleus where it is degraded. The volume of this flow determines the steady state concentration of Smad2 in the nucleus and this is used by cells to interpret extracellular morphogen concentration.
Cdx1andCdx2have overlapping functions in anteroposterior patterning and posterior axis elongation
Authors: van den Akker Eric , Forlani Sylvie , Chawengsaksophak Kallayanee , de Graaff Wim , Beck Felix , Meyer Barbara I. , Deschamps Jacqueline
Published: April 2021

Mouse Cdx and Hox genes presumably evolved from genes on a common ancestor cluster involved in anteroposterior patterning. Drosophila caudal (cad) is involved in specifying the posterior end of the early embryo, and is essential for patterning tissues derived from the most caudal segment, the analia. Two of the three mouse Cdx paralogues, Cdx 1 and Cdx2, are expressed early in a Hox-like manner in the three germ layers. In the nascent paraxial mesoderm, both genes are expressed in cells contributing first to the most rostral, and then to progressively more caudal parts of the vertebral column. Later, expression regresses from the anterior sclerotomes, and is only maintained for Cdx1 in the dorsal part of the somites, and for both genes in the tail bud. Cdx1 null mutants show anterior homeosis of upper cervical and thoracic vertebrae. Cdx2-null embryos die before gastrulation, and Cdx2 heterozygotes display anterior transformations of lower cervical and thoracic vertebrae. We have analysed the genetic interactions between Cdx1 and Cdx2 in compound mutants. Combining mutant alleles for both genes gives rise to anterior homeotic transformations along a more extensive length of the vertebral column than do single mutations. The most severely affected Cdx1 null/Cdx2 heterozygous mice display a posterior shift of their cranio-cervical, cervico-thoracic, thoraco-lumbar, lumbo-sacral and sacro-caudal transitions. The effects of the mutations in Cdx1 and Cdx2 were co-operative in severity, and a more extensive posterior shift of the expression of three Hox genes was observed in double mutants. The alteration in Hox expression boundaries occurred early. We conclude that both Cdx genes cooperate at early stages in instructing the vertebral progenitors all along the axis, at least in part by setting the rostral expression boundaries of Hox genes. In addition, Cdx mutants transiently exhibit alterations in the extent of Hox expression domains in the spinal cord, reminding of the strong effects of overexpressing Cdx genes on Hox gene expression in the neurectoderm. Phenotypical alterations in the peripheral nervous system were observed at mid-gestation stages. Strikingly, the altered phenotype at caudal levels included a posterior truncation of the tail, mildly affecting Cdx2 heterozygotes, but more severely affecting Cdx1/Cdx2 double heterozygotes and Cdx1 null/Cdx2 heterozygotes. Mutations in Cdx1 and Cdx2 therefore also interfere with axis elongation in a cooperative way. The function of Cdx genes in morphogenetic processes during gastrulation and tail bud extension, and their relationship with the Hox genes are discussed in the light of available data in Amphioxus, C. elegans, Drosophila and mice.
GATA6 regulates differentiation of distal lung epithelium
Authors: Yang Honghua , Lu Min Min , Zhang Lili , Whitsett Jeffrey A. , Morrisey Edward E.
Published: April 2021

GATA6 is a member of the GATA family of zinc-finger transcriptional regulators and is the only known GATA factor expressed in the distal epithelium of the lung during development. To define the role that GATA6 plays during lung epithelial cell development, we expressed a GATA6-Engrailed dominant-negative fusion protein in the distal lung epithelium of transgenic mice. Transgenic embryos lacked detectable alveolar epithelial type 1 cells in the distal airway epithelium. These embryos also exhibited increased Foxp2 gene expression, suggesting a disruption in late alveolar epithelial differentiation. Alveolar epithelial type 2 cells, which are progenitors of alveolar epithelial type 1 cells, were correctly specified as shown by normal thyroid transcription factor 1 and surfactant protein A gene expression. However, attenuated endogenous surfactant protein C expression indicated that alveolar epithelial type 2 cell differentiation was perturbed in transgenic embryos. The number of proximal airway tubules is also reduced in these embryos, suggesting a role for GATA6 in regulating distal-proximal airway development. Finally, a functional role for GATA factor function in alveolar epithelial type 1 cell gene regulation is supported by the ability of GATA6 to trans-activate the mouse aquaporin-5 promoter. Together, these data implicate GATA6 as an important regulator of distal epithelial cell differentiation and proximal airway development in the mouse.
Broad specifies pupal development and mediates the ‘status quo’ action of juvenile hormone on the pupal-adult transformation inDrosophilaandManduca
Authors: Zhou Xiaofeng , Riddiford Lynn M.
Published: April 2021

The understanding of the molecular basis of the endocrine control of insect metamorphosis has been hampered by the profound differences in responses of the Lepidoptera and the Diptera to juvenile hormone (JH). In both Manduca and Drosophila, the broad (br) gene is expressed in the epidermis during the formation of the pupa, but not during adult differentiation. Misexpression of BR-Z1 during either a larval or an adult molt of Drosophila suppressed stage-specific cuticle genes and activated pupal cuticle genes, showing that br is a major specifier of the pupal stage. Treatment with a JH mimic at the onset of the adult molt causes br re-expression and the formation of a second pupal cuticle in Manduca, but only in the abdomen of Drosophila. Expression of the BR isoforms during adult development of Drosophila suppressed bristle and hair formation when induced early or redirected cuticle production toward the pupal program when induced late. Expression of BR-Z1 at both of these times mimicked the effect of JH application but, unlike JH, it caused production of a new pupal cuticle on the head and thorax as well as on the abdomen. Consequently, the ‘status quo’ action of JH on the pupal-adult transformation is mediated by the JH-induced re-expression of BR.
Exogenous growth factors induce the production of ganglion cells at the retinal margin
Authors: Fischer Andy J. , Dierks Blair D. , Reh Thomas A.
Published: April 2021

Neural progenitors at the retinal margin of the post-hatch chicken normally produce amacrine and bipolar cells, but not photoreceptor or ganglion cells. The purpose of this study was to test whether exogenous growth factors influence the types of cells produced by progenitors at the retinal margin. We injected insulin, FGF2 or a combination of insulin and FGF2 into the vitreous chamber of post-hatch chickens. To assay for growth factor-induced changes at the retinal margin, we used in situ hybridization and immunocytochemistry on cryosections. One day after the final injection, we found that insulin alone stimulated the addition of cells to the retinal margin, but this was not further increased when FGF2 was applied with insulin. Insulin alone increased the number of cells in the progenitor zone that expressed neurofilament, and this was further increased when FGF2 was applied with insulin. These neurofilament-expressing cells in the progenitor zone included differentiating neurons that expressed Islet1 or Hu. Four days after the final dose of growth factor, we found that the production of ganglion cells was induced by co-injection of insulin and FGF2, but not by either insulin or FGF2 alone. We conclude that the types of cells produced by progenitors at the retinal margin can be altered by exogenous growth factors and that normally the microenvironment imposes limitations on the types of neurons produced.
A crucial role of β1 integrins for keratinocyte migration in vitro and during cutaneous wound repair
Authors: Grose Richard , Hutter Caroline , Bloch Wilhelm , Thorey Irmgard , Watt Fiona M. , Fässler Reinhard , Brakebusch Cord , Werner Sabine
Published: April 2021

Integrins are ubiquitous transmembrane receptors that play crucial roles in cell-cell and cell-matrix interactions. In this study, we have determined the effects of the loss of β1 integrins in keratinocytes in vitro and during cutaneous wound repair. Flow cytometry of cultured β1-deficient keratinocytes confirmed the absence of β1 integrins and showed downregulation of α6β4 but not of αv integrins. β1-null keratinocytes were characterised by poor adhesion to various substrates, by a reduced proliferation rate and by a strongly impaired migratory capacity. In vivo, the loss of β1 integrins in keratinocytes caused a severe defect in wound healing. β1-null keratinocytes showed impaired migration and were more densely packed in the hyperproliferative epithelium. Surprisingly, their proliferation rate was not reduced in early wounds and even increased in late wounds. The failure in re-epithelialisation resulted in a prolonged inflammatory response, leading to dramatic alterations in the expression of important wound-regulated genes. Ultimately, β1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate a crucial role of β1 integrins in keratinocyte migration and wound re-epithelialisation.

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The inhibition of cell aggregation by a pure serum protein
Authors: Curtis A. S. G. , Greaves M. F.
Published: April 2021

The aggregation of isolated cells into coherent multicellular bodies is widely thought to be due mainly if not entirely to the adhesiveness of the cells for one another, according to Moscona (1961a, b), Curtis (1962) and Steinberg (1962a) amongst others. In consequence the aggregation of cells from dispersed (disaggregated) tissues has been widely used as a test for the degree of adhesiveness shown by the cells, and conditions affecting aggregation have been interpreted as affecting cell adhesion. Using this type of test Moscona (1961a, b) found that embryonic chick cells would not aggregate at temperatures below 14° C. It was also discovered that aggregation was inhibited at 37° C. by puromycin and actinomycin D (Moscona & Moscona, 1963), by glucosamine-HCl (Garber, 1963), and by chloramphenicol (Nakanishi et al., 1963). Moscona concluded from the failure of aggregation at low temperatures that the metabolic synthesis of an adhesive substance was being prevented under such conditions and this interpretation was reinforced by the evidence of chemical inhibition of aggregation. Moscona (1962) suggested that the adhesive substance was responsible for producing cell to cell adhesion. In all these experiments cells were aggregated in media containing serum, usually horse serum.
Studies on some aspects of the rôle of sulfhydryl groups in morphogenesis
Authors: Mulherkar Leela , Rao K. Vasudeva , Joshi Sanjivani S.
Published: April 2021

The importance of sulfhydryl compounds in the process of morphogenesis was pointed out by Brachet (1950). Using specific inhibitors of -SH such as chloroacetophenone, it has been shown that embryos develop a number of malformations when the activity of -SH groups is interfered with (Beatty, 1951; Deuchar, 1957; Lakshmi, 1962a). It has been observed that the abnormalities are mainly in the nervous system and these findings are in agreement with the distribution of -SH groups in embryos of amphibia (Brachet, 1950) and chick (Rulon, 1935). These studies have vindicated the importance of -SH containing proteins stressed by Brachet. In the present report are described some studies using chloroacetophenone (CAP) as an -SH inhibitor and cysteine to reverse its action.
Ultrastructure of the blastopore cells in the newt
Authors: Perry Margaret M. , Waddington C. H.
Published: April 2021

Longitudinal and transverse sections of the flask-shaped blastopore cells in the early gastrula of Triturus alpestris have been examined in the electron microscope. The cytoplasm may be divided into three main regions; a distal, superficial, granular zone; a vesicular and, more proximally, a pigment zone in the necks; and the main body of the cell with nucleus, yolk platelets and lipid droplets. A thin, continuous dense layer of extracellular material covers the cells at the free surface. Numerous microtubules oriented parallel to the main axes are found grouped in the necks. Other prominent organelles are vesicles, which from their structure have been divided into three categories, the alpha, beta and gamma vesicles. Longitudinal flanges extending along the necks are complexly interwound with those of adjacent cells and bind the cells firmly together in this region. Neither the extracellular layer, nor the superficial granular layer, is considered to exert a contractile force which would cause the cells to become elongated; rather the change in shape is brought about by active elongation within the internal cytoplasm, in which the microtubular system plays an important part. The material in the cell tips probably results from the passive accumulations of substances which originally covered a larger surface area. The alpha vesicles are common to all cells in the embryo, whereas the beta and gamma vesicles are characteristic of the blastopore cells. The function of these organelles is at present unknown, although there are some structural similarities between the beta vesicles and lysosomal particles described in other organisms.
Whisker growth after removal of the dermal papilla and lengths of follicle in the hooded rat
Authors: Oliver R. F.
Published: April 2021

The arrangement and mode of growth of the major vibrissae on the upper lip of the hooded rat has been studied. There was an antero-posterior gradation in rates of growth and club lengths produced in each of the vertical rows. The longest vibrissae were produced at the fastest rate in the larger follicles in the posterior vertical rows. There was a similar antero-posterior gradation in the times for a phase of growth throughout each of the vertical rows. There are no overall waves of growth on the upper lip; phases of growth are entered into by the vertical rows individually. The suggestion is made that the above behaviour may be related to the mode of development of the vibrissae in the embryo. A method has been described for the removal of the dermal papilla in situ and the removal of dermal papillae and various lengths of whisker root (‘root ends’) have been performed to determine the effects of these operations on whisker growth. After removal of dermal papillae, all 18 follicles produced generations of whiskers; 15 of these follicles produced vibrissae of normal or nearly normal length. After removal of root ends, whiskers of shorter than normal length were produced from 28 out of 37 follicles. Conclusive evidence was obtained that generations of vibrissae can be produced after complete removal of the dermal papilla. The degree of regeneration, as expressed by the length of post-operative whiskers produced, was apparently dependent on the amount of proximal follicle root removed.
Osteogenesis in transplants of bone marrow cells
Authors: Friedenstein A. J. , Piatetzky-Shapiro I. I. , Petrakova K. V.
Published: April 2021

After heterotopic (e.g. subcutaneous) transplantation of bone marrow, haemopoiesis in the graft ceases; reticular tissue develops instead, and later bone is formed (Denis, 1958). The result can be achieved by grafting either free pieces of bone marrow or those placed in diffusion chambers (Petrakova, Tolmacheva & Friedenstein, 1963; Rosin, Freiberg & Sajnek, 1963). In the case of free transplantation the bone formed is later filled with bone marrow. After transplantation in diffusion chambers haemopoiesis does not recur despite the development of a considerable mass of bone in the chambers (Friedenstein, 1965).
The development of the chick embryo diencephalon and mesencephalon during the initial phases of neuroblast differentiation
Authors: Lyser Katherine M.
Published: April 2021

The development of the nervous system presents many interesting problems as a developing system with numerous parameters of differentiation as well as from the point of view of the establishment of adult structure and function. With our growing understanding of developmental processes in general, and interactions at various stages of development in particular, it should be profitable to study more closely events of each period in a developing system, looking for information concerning their immediate control and their relation to events of other periods. In the nervous system, one phase which should be investigated much more thoroughly—especially from the point of view of the control of cellular differentiation—is that of the initial appearance of neuroblast cells and formation of the first nerve processes. Most studies of normal embryos which have included the period of initial differentiation have been primarily concerned with tracing the origins of definitive nuclei and fiber tracts, though possible mechanisms controlling various aspects of their development have of course been discussed.
The influence of the area opaca on the development of the young chick embryo
Authors: Bellairs Ruth , Bromham D. R. , Wylie C. C.
Published: April 2021

The effects exerted by the area opaca upon the area pellucida have been tested experimentally by interfering with the normal relationships between them and then growing the blastoderm in tissue culture by the technique of New. If the entire area opaca was removed from a blastoderm at the full-length primitive streak stage, the embryo that formed was smaller than the controls and poorly differentiated. New evidence supporting the hypothesis that the area opaca influences the development of the embryo by exerting a tension upon the area pellucida is presented. Estimates of the mitotic rates provided no evidence to support the idea that this centrifugal tension promoted a high rate of cell division. With reduction in tension, however, cell death increased. No evidence could be found to suggest that the isolated area pellucida failed to grow and differentiate because its cell population was inadequate. When three area pellucidae were cultured in close contact with one another, growth and differentiation were no better than when one was cultured alone. The hypothesis that the proximal part of the area opaca exerted a nutritive effect on the area pellucida was tested. This was supported by the fact that when the area pellucida was explanted on top of the area opaca, differentiation of the embryo was good. Furthermore, some digestion of the area opaca endoderm appeared to take place. On the other hand, such a relationship cannot be essential for development at this stage, since equally good development could occur when the proximal part of the area opaca had been removed.
Somite segmentation in amphibian embryos: is there a transmitted control mechanism?
Authors: Deuchar E. M. , Burgess A. M. C.
Published: April 2021

In all vertebrate embryos, somite segmentation begins in the occipital region and proceeds from here caudally with remarkable regularity. The segmentation pattern and the shape, size and number of somites formed are constant for each species, and it appears as if some quite complex mechanism must control their development. That this control mechanism must be versatile as well as precise is shown, for instance, by the fact that haploid newts have a larger number of cells per somite than the normal diploid, while polyploids have smaller numbers of somite cells than normal, so that the somite sizes are very nearly the same in all cases: the number of somites per embryo is also always the same as in the diploid (Fankhauser, 1945). Further, when mesoderm is either added to or excised from the somite region of the archenteron roof experimentally (Waddington & Deuchar, 1953), there is regulation so that the overall shape of the somites remains nearly normal, and again, their number per embryo is unchanged from that typical of the species.
Extra-toes:a new mutant gene causing multiple abnormalities in the mouse
Authors: Johnson D. R.
Published: April 2021

Extra-toes (Xt) is a new semi-dominant gene in the mouse. Xt/Xt animals die in utero or at birth. They have multiple abnormalities including paddle-shaped feet with up to eight or nine digits, hemimelia, disturbed spinal cord and brain, nose, eye and ear, and oedema. The heterozygote has pre- and post-axial polydactylism of all four feet. The Extra-toes homozygote can first be recognized as a 9-day embryo by excessively large pharyngeal arches and persistently open neural tube. Many abnormalities of the brain and sense organs can be traced back to malformation of the neural tube. Malformations of the upper jaw region and limbs can be traced back to overgrowth from the 9-day stage onwards. A third series of malformations due to oedema (first seen at 13 days) is described. The possible interrelations of these three groups of abnormalities to each other, and the relationship of the Xt syndrome to other gene effects in the mouse, chicken and guinea-pig are discussed.
Les facteurs de polarisation dans les premiers stades du développement chezParascaris equorum
Authors: Guerrier Par Pierre
Published: April 2021

Le développement de Parascaris equorum comporte une détermination très stricte ainsi que de faibles capacités de régulation. Celles-ci s’éteignent dès l’achèvement du premier clivage (Nigon, 1965). Il ressortait d’une étude antérieure (Nigon, Guerrier & Monin, 1960) que ces caractères pourraient être mis en rapport avec l’établissement, peu avant la première division de segmentation, d’une structuration corticale relativement stable. Le présent travail a été entrepris afin de tester cette hypothèse. Un bref rappel permettra de situer les circonstances dans lesquelles se dessinent les déterminations étudiées.
Recherches sur l'inhibition de la régénération du pharynx chez les planaires
Authors: Ziller-Sengel Catherine
Published: April 2021

L’idée que toute morphogenèse doit son accomplissement harmonieux non seulement à des facteurs positifs, les inductions, mais également à des facteurs négatifs, les actions inhibitrices, est relativement ancienne et très répandue. Elle s’appuie sur des données expérimentales aussi nombreuses que variées, tant dans le domaine de l’embryogenèse que dans celui de la régénération et chez des espèces animales très variées.
A quantitative study of the number and distribution of neoblasts in Dugesia lugubris (Planaria) with reference to size and ploidy
Authors: Lange C. S.
Published: April 2021

This paper reports observations on the number of neoblasts in diploid and triploid planarian biotypes, the relation of this number to the size of the animal and the distribution of neoblasts with respect to the long axis of the animal. The number of neoblasts is a function of animal length for both diploid and triploid biotypes, but no significant difference was found between the biotypes. The combined data yield a regression equation of log. (number of neoblasts) = 1·90 log. (length) + 3·47. The distribution of neoblasts with respect to the long axis of the planarian was found to have two relative maxima, one anterior and one posterior to the intercalary minimum associated with the pharyngeal region of the animal. The relative position of the pharynx remains unchanged with growth in the triploid animal, in contradistinction to the progressive shift cephalad in the diploid. As statistical analysis showed no significant difference in the effects of the histological methods employed on the two biotypes, this observation is interpreted as a demonstration of different modes of growth in the diploid and the triploid. The volume of the planarian (in the fixed state) was correlated with the animal’s length (when alive) to yield a regression equation of log. (volume) = 2·62 log. (length) + 5·70. The slope of this regression equation is highly significantly different from that of the neoblast regression line. Thus larger animals have a lower density of neoblasts, although more of them. It is suggested that this latter observation may have some bearing on the problem of senescence in planarians. Counts of objects in serial sections are subject to an overestimate which can be corrected by the method of Abercrombie. This method, however, is based on an assumption which is not always valid. Therefore a more rigorous correction formula has been derived. This formula was then applied to the measurement of neoblast nuclear diameters (in the fixed state). No significant difference was found for nuclear diameters of diploid and triploid neoblasts.
Hox genes and growth: early and late roles in limb bud morphogenesis
Authors: Morgan Bruce A. , Tabin Cliff
Published: April 2021

In recent years, molecular analysis has led to the identification of some of the key genes that control the morphogenesis of the developing embryo. Detailed functional analysis of these genes is rapidly leading to a new level of understanding of how embryonic form is regulated. Understanding the roles that these genes play in development can additionally provide insights into the evolution of morphology.

The 5′ genes of the vertebrate Hox clusters are expressed in complex patterns during limb morphogenesis. Various models suggest that the Hoxd genes specify positional identity along the anteroposterior (A-P) axis of the limb. Close examination of the pattern of Hoxd gene expression in the limb suggests that a distinct combination of Hoxd gene expressed in different digit primordia is unlikely to specify each digit independently. The effects of altering the pattern of expression of the Hoxd-11 gene at different times during limb development indicate that the Hoxd genes have separable early and late roles in limb morphogenesis. In their early role, the Hoxd genes are involved in regulating the growth of the undifferentiated limb mesenchyme. Restriction of the expression of successive 5’ Hoxd genes to progressively more posterior regions of the bud results in the asymmetric outgrowth of the limb mesenchyme. Later in limb development, Hoxd genes also regulate the maturation of the nascent skeletal elements. The degree of overlap in function between different Hoxd genes may be different in these early and late roles. The combined action of many Hox genes on distinct developmental processes contribute to pattern asymmetry along the A-P axis.
The Effect of Cortisone on Cell Proliferation and Migration in Peripheral Nerves undergoing Wallerian degeneration
Authors: Thomas G. A.
Published: April 2021

The administration of 10 mg. of cortisone per day to rabbits caused a depression in the proliferation of all the cells in nerves undergoing Wallerian degeneration. The increase in numbers of cells within Schwann tubes was most affected, that of the endoneurial connective tissue cells and of the cells of the blood-vessel wall less. A greater depression of population occurred at the 10th day of degeneration than at the 20th or 25th. In vitro fewer cells migrated from expiants of degenerating peripheral nerves from animals receiving cortisone than from degenerating nerves from control animals, but the difference is accounted for by different numbers of cells in the expiants.
The Embryology of the Telencephalic Fibre Systems in the Mouse
Authors: Källén Bengt
Published: April 2021

The ontogeny of the fibres in the telencephalon of Mus musculus has been studied. Reconstructions have been made using seven different stages. The formation of some telencephalic and diencephalic fascicles is described. The agreement supposed by Shaner (1936) to exist between the phylogeny and ontogeny of the fascicles is not supported by the present investigation. The migration areas and migration layers can develop before the fibre fascicles are formed, and thus without any influence from them. The division of the migration layers into nuclei takes place simultaneously with the entrance of the fibres into the layers, and hence a causal relation may exist between these two processes. The fibre anatomy may be of some importance with regard to establishing the homologies of the late subdivisions of the migration layers. The spaces between the migration areas and layers seem to act as pathways for the outgrowing neurites. The migration areas, which are also proliferation centres, seem to attract the neurites.
Morphogénèse de Bipartition chez Urocentrum Turbo (Cilié Holotriche)
Authors: Fauré-Fremiet E.
Published: April 2021

Different species of Ciliates are characterized by the relative positions of the meridional ciliary bands (somatic kineties) and the oral or peristomial ciliary bands. Division sees the formation of two homothetic ciliary systems, one defining the anterior individual (proter) and the other the posterior individual (opisthe). Urocentrum turbo is characterized by the secondary arrangement of its somatic kinetosomes on transverse annular lines forming a wide anterior girdle or fascia and a narrow equatorial girdle or cingula. At the first stage of division the cingula grows by the multiplication of its kinetosomes; the distribution of these along the somatic kineties then completes the morphogenesis of the proter and opisthe. The cingula of Urocentrum is a morphogenic zone which conforms in its actual structure to the provisional idea of a ‘division zone’ introduced by Calkins. The oral ciliation constitutes an autonomous system with its own morphogenic zone.
Fecundity and Embryonic Mortality in Pigs
Authors: Perry J. S.
Published: April 2021

863 female pigs, mostly sows discarded from commercial herds in East Anglia and sold for slaughter, were examined when killed and the condition of the reproductive tract was related to the animal’s reproductive history when it was known. The most frequent number of corpora lutea was 20, the average 19·6. Nineteen pigs pregnant for the first time (gilts) had an average of 13·6 corpora lutea and 9·8 embryos; 83 in their second or subsequent pregnancies (sows) averaged 19·25 corpora lutea and 11·9 embryos. The average number of corpora lutea (ovulations) rose sharply after the first litter, continued to rise slightly until after the fourth litter, and rose again after the fifth. The initial rise and subsequent upward trend for several litters is similar to what has been recorded elsewhere for the litter size at birth, but the increasing number of ovulations in later life is in contrast with the falling off which has been observed in the size of the litter at birth. If both occur in the same population, as seems likely, there must be a substantial increase in embryonic mortality in the later litters. The percentage of ova lost between ovulation and the time of observation was greater in parous than in nulliparous animals, but the difference was found to be attributable to the greater initial size of litters in sows, large litters being found to lose proportionately more ova than small ones. Five of 19 gilts and 4 of 83 sows showed no loss of ova. At least 40 per cent, of all ova ovulated are lost before parturition. About 85 per cent, of the loss is incurred in the first half of gestation, and something like three-quarters of it is incurred before the 25th day of pregnancy. It is suggested that most of the embryonic loss probably occurs at or about the time of implantation between the 10th and 20th day. Even in the case of the largest litters there is no evidence of heavy loss in late stages of pregnancy that could be attributed to the sow’s inability to accommodate or nourish the foetuses.
The Incorporation of Labelled Amino-acids into Amphibian Embryos
Authors: Waddington C. H. , Sirlin J. L.
Published: April 2021

The rate of incorporation of glycine-l-C14 into the tissues of X enopus tailbud embryos was estimated by counting grains in autoradiographs. The tissues differed significantly, the order of activity being epidermis > somitic mesoderm > neural tube > notochord > endoderm. Less precise data indicated that the incorporation both of glycine-l-C14 and methionine-S35 is more rapid into the nuclei than the cytoplasm, and that there may be some differential accumulation also in the cell membranes. The rate of accumulation of glycine-2-C14 in acid- and acetone-insoluble material, estimated by the Geiger counter, is reduced in the presence of the amino-acid analogue p-fluoro-phenyl-alanine. This effect is counteracted by L-phenyl-alanine.
Teratological studies with sulphonamides and their implications
Authors: Landauer Walter , Wakasugi Noboru
Published: April 2021

It is one of the principal aims of teratological research to trace the manner in which particular chemical compounds give rise to abnormal phenotypes by interfering with well-defined metabolic events. Problems that seemed to lend themselves to investigations of this nature arose with the discovery that malformations can be produced by sulphonamides, which in clinical practice are or have been used as inhibitors of carbonic anhydrase and the activity of which was considered to be quite specific in that respect. We had earlier reported on the effects which one such compound has on developing chicken embryos and shall now describe results obtained with three further sulphonamides. We shall then attempt to discuss the meaning of these and related data in terms of general teratological problems.
Studies of the cleavage in the frog egg: II. On determination of the position of the furrow
Authors: Kubota T.
Published: April 2021

Tn sea-urchin eggs, once karyokinesis reaches metaphase or anaphase, the cleavage furrow can be formed even if the mitotic apparatus is destroyed (Swann & Mitchison, 1953) or removed (Hiramoto, 1956). A similar result was obtained in frog eggs (Kubota, 1966). In amphibian eggs a much longer time is available for performing experiments than in sea urchins as the furrow first appears at the animal pole and slowly travels toward the vegetal pole. Taking advantage of this situation, Waddington (1952) and Dan & Kuno-Kojima (1963) performed various kinds of operations to elucidate the roles of the egg cortex and the inner cytoplasm in furrow formation, and Selman & Waddington (1955) also made cytological observations of the process.
The induction of hair follicle formation in the adult hooded rat by vibrissa dermal papillae
Authors: Oliver R. F.
Published: April 2021

Hair follicles are essentially composed of two tissues. The inner epidermal component, which gives rise to, among other products, the keratinized hair shaft, is confluent with the surface epidermis and is ensheathed by the dermal component which is confluent with the pars papillaris of the dermis.