bluuebunny/crossref_metadata_2025 huggingface dataset:
The Abruptex domain of Notch regulates negative interactions between Notch, its ligands and Fringe
Authors: Celis Jose F. de , Bray Sarah J.
Published: April 2021

The Notch signalling pathway regulates cell fate choices during both vertebrate and invertebrate development. In the Drosophila wing disc, the activation of Notch by its ligands Delta and Serrate is required to make the dorsoventral boundary, where several genes, such as wingless and cut, are expressed in a 2-to 4-cell-wide domain. The interactions between Notch and its ligands are modulated by Fringe via a mechanism that may involve post-transcriptional modifications of Notch. The ligands themselves also help to restrict Notch activity to the dorsoventral boundary cells, because they antagonise the activation of the receptor in the cells where their expression is high. This function of the ligands is critical to establish the polarity of signalling, but very little is known about the mechanisms involved in the interactions between Notch and its ligands that result in suppression of Notch activity. The extracellular domain of Notch contains an array of 36 EGF repeats, two of which, repeats 11 and 12, are necessary for direct interactions between Notch with Delta and Serrate. We investigate here the function of a region of the Notch extracellular domain where several missense mutations, called Abruptex, are localised. These Notch alleles are characterised by phenotypes opposite to the loss of Notch function and also by complex complementation patterns. We find that, in Abruptex mutant discs, only the negative effects of the ligands and Fringe are affected, resulting in the failure to restrict the expression of cut and wingless to the dorsoventral boundary. We suggest that Abruptex alleles identify a domain in the Notch protein that mediates the interactions between Notch, its ligands and Fringe that result in suppression of Notch activity.
Control of hindbrain motor neuron differentiation by the homeobox genePhox2b
Authors: Pattyn Alexandre , Hirsch Marie-Rose , Goridis Christo , Brunet Jean-François
Published: April 2021

Motor neurons are a widely studied model of vertebrate neurogenesis. They can be subdivided in somatic, branchial and visceral motor neurons. Recent studies on the dorsoventral patterning of the rhombencephalon have implicated the homeobox genes Pax6 and Nkx2.2 in the early divergence of the transcriptional programme of hindbrain somatic and visceral motor neuronal differentiation. We provide genetic evidence that the paired-like homeodomain protein Phox2b is required for the formation of all branchial and visceral, but not somatic, motor neurons in the hindbrain. In mice lacking Phox2b, both the generic and subtype-specific programs of motoneuronal differentiation are disrupted at an early stage. Most motor neuron precursors die inside the neuroepithelium while those that emigrate to the mantle layer fail to switch on early postmitotic markers and to downregulate neuroepithelial markers. Thus, the loss of function of Phox2b in hindbrain motor neurons exemplifies a novel control point in the generation of CNS neurons.
The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo
Authors: Camus Anne , Davidson Bruce P. , Billiards Saraid , Khoo Poh-Lynn , Rivera-Pérez Jaime A. , Wakamiya Maki , Behringer Richard R. , Tam Patrick P. L.
Published: April 2021

The anterior midline tissue (AML) of the late gastrula mouse embryo comprises the axial mesendoderm and the ventral neuroectoderm of the prospective forebrain, midbrain and rostral hindbrain. In this study, we have investigated the morphogenetic role of defined segments of the AML by testing their inductive and patterning activity and by assessing the impact of their ablation on the patterning of the neural tube at the early-somite-stage. Both rostral and caudal segments of the AML were found to induce neural gene activity in the host tissue; however, the de novo gene activity did not show any regional characteristic that might be correlated with the segmental origin of the AML. Removal of the rostral AML that contains the prechordal plate resulted in a truncation of the head accompanied by the loss of several forebrain markers.

However, the remaining tissues reconstituted Gsc and Shh activity and expressed the ventral forebrain marker Nkx2.1. Furthermore, analysis of Gsc-deficient embryos reveals that the morphogenetic function of the rostral AML requires Gsc activity. Removal of the caudal AML led to a complete loss of midline molecular markers anterior to the 4th somite. In addition, Nkx2.1 expression was not detected in the ventral neural tube. The maintenance and function of the rostral AML therefore require inductive signals emanating from the caudal AML. Our results point to a role for AML in the refinement of the anteroposterior patterning and morphogenesis of the brain.
Basic fibroblast growth factor positively regulates hematopoietic development
Authors: Faloon Patrick , Arentson Elizabeth , Kazarov Alexander , Deng Chu Xia , Porcher Catherine , Orkin Stuart , Choi Kyunghee
Published: April 2021

Recently identified BLast Colony Forming Cells (BL-CFCs) from in vitro differentiated embryonic stem (ES) cells represent the common progenitor of hematopoietic and endothelial cells, the hemangioblast. Access to this initial cell population committed to the hematopoietic lineage provides a unique opportunity to characterize hematopoietic commitment events. Here, we show that BL-CFC expresses the receptor tyrosine kinase, Flk1, and thus we took advantage of the BL-CFC assay, as well as fluorescent activated cell sorter (FACS) analysis for Flk1+ cells to determine quantitatively if mesoderm-inducing factors promote hematopoietic lineage development. Moreover, we have analyzed ES lines carrying targeted mutations for fibroblast growth factor receptor-1 (fgfr1), a receptor for basic fibroblast growth factor (bFGF), as well as scl, a transcription factor, for their potential to generate BL-CFCs and Flk1+ cells, to further define events leading to hemangioblast development. Our data suggest that bFGF-mediated signaling is critical for the proliferation of the hemangioblast and that cells expressing both Flk1 and SCL may represent the hemangioblast.
MAPK signaling by the D quadrant embryonic organizer of the mollusc Ilyanassa obsoleta
Authors: Lambert J. David , Nagy Lisa M.
Published: April 2021

Classical experiments performed on the embryo of the mollusc Ilyanassa obsoleta demonstrate that the 3D macromere acts as an embryonic organizer, by signaling to other cells and inducing them to assume the correct pattern of cell fates. We have discovered that MAP kinase signaling is activated in the cells that require the signal from 3D for normal differentiation. Preventing specification of the D quadrant lineage by removing the polar lobe disrupts the pattern of MAPK activation, as does ablation of the 3D macromere itself. Blocking MAPK activation with the MAP Kinase inhibitor U0126 produces larvae that differentiate the same limited complement of tissues as D quadrant deletions. Our results suggest that the MAP Kinase signaling cascade transduces the inductive signal from 3D and specifies cell fate among the cells that receive the signal.
The ASYMMETRIC LEAVES2 gene of Arabidopsis thaliana regulates formation of a symmetric lamina, establishment of venation and repression of meristem-related homeobox genes in leaves
Authors: Semiarti Endang , Ueno Yoshihisa , Tsukaya Hirokazu , Iwakawa Hidekazu , Machida Chiyoko , Machida Yasunori
Published: April 2021

The asymmetric leaves2 (as2) mutant of Arabidopsis thaliana generated leaf lobes and leaflet-like structures from the petioles of leaves in a bilaterally asymmetric manner. Both the delayed formation of the primary vein and the asymmetric formation of secondary veins were apparent in leaf primordia of as2 plants. A distinct midvein, which is the thickest vein and is located in the longitudinal center of the leaf lamina of wild-type plants, was often rudimentary even in mature as2 leaves. However, several parallel veins of very similar thickness were evident in such leaves. The complexity of venation patterns in all leaf-like organs of as2 plants was reduced. The malformed veins were visible before the development of asymmetry of the leaf lamina and were maintained in mature as2 leaves. In vitro culture on phytohormone-free medium of leaf sections from as2 mutants and from the asymmetric leaves1 (as1) mutant, which has a phenotype similar to that of as2, revealed an elevated potential in both cases for regeneration of shoots from leaf cells. Analysis by the reverse transcription-polymerase chain reaction showed that transcripts of the KNAT1, KNAT2 and KNAT6 (a recently identified member of the class 1 knox family) genes accumulated in the leaves of both as2 and as1 plants but not of wild type. Transcripts of the STM gene also accumulated in as1 leaves. These findings suggest that, in leaves, the AS2 and AS1 genes repress the expression of these homeobox genes, which are thought to maintain the indeterminate cell state in the shoot apical meristem. Taken together, our results suggest that AS2 and AS1 might be involved in establishment of a prominent midvein and of networks of other veins as well as in the formation of the symmetric leaf lamina, which might be related to repression of class 1 knox homeobox genes in leaves.
Gene expression profiles inCiona intestinalistailbud embryos
Authors: Satou Yutaka , Takatori Naohito , Yamada Lixy , Mochizuki Yasuaki , Hamaguchi Makoto , Ishikawa Hisayoshi , Chiba Shota , Imai Kaoru , Kano Shungo , Murakami Seiko D. , Nakayama Akie , Nishino Atsuo , Sasakura Yasunori , Satoh Gohki , Shimotori Taishin , Shin-i Tadasu , Shoguchi Eiichi , Suzuki Miho M. , Takada Norio , Utsumi Nanami , Yoshida Natsue , Saiga Hidetoshi , Kohara Yuji , Satoh Nori
Published: April 2021

A set of 3423 expressed sequence tags derived from the Ciona intestinalis tailbud embryos was categorized into 1213 independent clusters. When compared with DNA Data Bank of Japan database, 502 clusters of them showed significant matches to reported proteins with distinct function, whereas 184 lacked sufficient information to be categorized (including reported proteins with undefined function) and 527 had no significant similarities to known proteins. Sequence similarity analyses of the 502 clusters in relation to the biosynthetic function, as well as the structure of the message population at this stage, demonstrated that 390 of them were associated with functions that many kinds of cells use, 85 with cell-cell communication and 27 with transcription factors and other gene regulatory proteins. All of the 1213 clusters were subjected to whole-mount in situ hybridization to analyze the gene expression profiles at this stage. A total of 387 clusters showed expression specific to a certain tissue or organ; 149 showed epidermis-specific expression; 34 were specific to the nervous system; 29 to endoderm; 112 to mesenchyme; 32 to notochord; and 31 to muscle. Many genes were also specifically expressed in multiple tissues. The study also highlighted characteristic gene expression profiles dependent on the tissues. In addition, several genes showed intriguing expression patterns that have not been reported previously; for example, four genes were expressed specifically in the nerve cord cells and one gene was expressed only in the posterior part of muscle cells.

This study provides molecular markers for each of the tissues and/or organs that constitutes the Ciona tailbud embryo. The sequence information will also be used for further genome scientific approach to explore molecular mechanisms involved in the formation of one of the most primitive chordate body plans.
Hunchback is required for the specification of the early sublineage of neuroblast 7-3 in theDrosophilacentral nervous system
Authors: Novotny Tanja , Eiselt Regina , Urban Joachim
Published: April 2021

The Drosophila ventral nerve cord (VNC) derives from neuroblasts (NBs), which mostly divide in a stem cell mode and give rise to defined NB lineages characterized by specific sets of sequentially generated neurons and/or glia cells. To understand how different cell types are generated within a NB lineage, we have focused on the NB7-3 lineage as a model system. This NB gives rise to four individually identifiable neurons and we show that these cells are generated from three different ganglion mother cells (GMCs). The finding that the transcription factor Hunchback (Hb) is expressed in the early sublineage of NB7-3, which consists of the early NB and the first GMC (GMC7-3a) and its progeny (EW1 and GW), prompted us to investigate its possible role in NB7-3 lineage development. Our analysis revealed that loss of hb results in a lack of the normally Hb-positive neurons, while the later-born neurons (designated as EW2 and EW3) are still present. However, overexpression of hb in the whole lineage leads to additional cells with the characteristics of GMC7-3a-derived neurons, at the cost of EW2 and EW3. Thus, hb is an important determinant in specifying early sublineage identity in the NB7-3 lineage. Using Even-skipped (Eve) as a marker, we have additionally shown that hb is also needed for the determination and/or differentiation of several other early-born neurons, indicating that this gene is an important player in sequential cell fate specification within the Drosophila CNS.
Math3andNeuroDregulate amacrine cell fate specification in the retina
Authors: Inoue Tomoyuki , Hojo Masato , Bessho Yasumasa , Tano Yasuo , Lee Jacqueline E. , Kageyama Ryoichiro
Published: April 2021

The basic helix-loop-helix genes Math3 and NeuroD are expressed by differentiating amacrine cells, retinal interneurons. Previous studies have demonstrated that a normal number of amacrine cells is generated in mice lacking either Math3 or NeuroD. We have found that, in Math3-NeuroD double-mutant retina, amacrine cells are completely missing, while ganglion and Müller glial cells are increased in number. In the double-mutant retina, the cells that would normally differentiate into amacrine cells did not die but adopted the ganglion and glial cell fates. Misexpression studies using the developing retinal explant cultures showed that, although Math3 and NeuroD alone only promoted rod genesis, they significantly increased the population of amacrine cells when the homeobox gene Pax6 or Six3 was co-expressed. These results indicate that Math3 and NeuroD are essential, but not sufficient, for amacrine cell genesis, and that co-expression of the basic helix-loop-helix and homeobox genes is required for specification of the correct neuronal subtype.
TheC. elegans even-skippedhomologue,vab-7, specifies DB motoneurone identity and axon trajectory
Authors: Esmaeili Behrooz , Ross Jennifer M. , Neades Cara , Miller David M. , Ahringer Julie
Published: April 2021

Locomotory activity is defined by the specification of motoneurone subtypes. In the nematode, C. elegans, DA and DB motoneurones innervate dorsal muscles and function to induce movement in the backwards or forwards direction, respectively. These two neurone classes express separate sets of genes and extend axons with oppositely directed trajectories; anterior (DA) versus posterior (DB). The DA-specific homeoprotein UNC-4 interacts with UNC-37/Groucho to repress the DB gene, acr-5 (nicotinic acetylcholine receptor subunit). We show that the C. elegans even-skipped-like homoedomain protein, VAB-7, coordinately regulates different aspects of the DB motoneurone fate, in part by repressing unc-4. Wild-type DB motoneurones express VAB-7, have posteriorly directed axons, express ACR-5 and lack expression of the homeodomain protein UNC-4. In a vab-7 mutant, ectopic UNC-4 represses acr-5 and induces an anteriorly directed DB axon trajectory. Thus, vab-7 indirectly promotes DB-specific gene expression and posteriorly directed axon outgrowth by preventing UNC-4 repression of DB differentiation. Ectopic expression of VAB-7 also induces DB traits in an unc-4-independent manner, suggesting that VAB-7 can act through a parallel pathway. This work supports a model in which a complementary pair of homeodomain transcription factors (VAB-7 and UNC-4) specifies differences between DA and DB neurones through inhibition of the alternative fates. The recent findings that Even-skipped transcriptional repressor activity specifies neurone identity and axon guidance in the mouse and Drosophila motoneurone circuit points to an ancient origin for homeoprotein-dependent mechanisms of neuronal differentiation in the metazoan nerve cord.
Larval optic nerve and adult extra-retinal photoreceptors sequentially associate with clock neurons duringDrosophilabrain development
Authors: Malpel Sébastien , Klarsfeld André , Rouyer François
Published: April 2021

The visual system is one of the input pathways for light into the circadian clock of the Drosophila brain. In particular, extra-retinal visual structures have been proposed to play a role in both larval and adult circadian photoreception. We have analyzed the interactions between extra-retinal structures of the visual system and the clock neurons during brain development. We first show that the larval optic nerve, or Bolwig nerve, already contacts clock cells (the lateral neurons) in the embryonic brain. Analysis of visual system-defective genotypes showed that the absence of the afferent Bolwig nerve resulted in a severe reduction of the lateral neurons dendritic arborization, and that the inhibition of nerve activity induced alterations of the dendritic morphology. During wild-type development, the loss of a functional Bolwig nerve in the early pupa was also accompanied by remodeling of the arborization of the lateral neurons. Approximately 1.5 days later, visual fibers that came from the Hofbauer-Buchner eyelet, a putative photoreceptive organ for the adult circadian clock, were seen contacting the lateral neurons. Both types of extra-retinal photoreceptors expressed rhodopsins RH5 and RH6, as well as the norpA-encoded phospholipase C. These data strongly suggest a role for RH5 and RH6, as well as NORPA, signaling in both larval and adult extra-retinal circadian photoreception. The Hofbauer-Buchner eyelet therefore does not appear to account for the previously described norpA-independent light input to the adult clock. This supports the existence of yet uncharacterized photoreceptive structures in Drosophila.
Calmodulin-dependent protein kinase IV mediated antagonism of BMP signaling regulates lineage and survival of hematopoietic progenitors
Authors: Walters Melinda J. , Wayman Gary A. , Notis John C. , Goodman Richard H. , Soderling Thomas R. , Christian Jan L.
Published: April 2021

In the current study, we show that bone morphogenetic proteins (BMPs) play a role in hematopoiesis that is independent of their function in specifying ventral mesodermal fate. When BMP activity is upregulated or inhibited in Xenopus embryos hematopoietic precursors are specified properly but few mature erythrocytes are generated. Distinct cellular defects underlie this loss of erythrocytes: inhibition of BMP activity induces erythroid precursors to undergo apoptotic cell death, whereas constitutive activation of BMPs causes an increase in commitment of hematopoietic progenitors to myeloid differentiation and a concomitant decrease in erythrocytes that is not due to enhanced apoptosis. These blood defects are observed even when BMP activity is misregulated solely in non-hematopoietic (ectodermal) cells, demonstrating that BMPs generate extrinsic signals that regulate hematopoiesis independent of mesodermal patterning. Further analysis revealed that endogenous calmodulin-dependent protein kinase IV (CaM KIV) is required to negatively modulate hematopoietic functions of BMPs downstream of receptor activation. Our data are consistent with a model in which CaM KIV inhibits BMP signals by activating a substrate, possibly cAMP-response element-binding protein (CREB), that recruits limiting amounts of CREB binding protein (CBP) away from transcriptional complexes functioning downstream of BMPs.
DrosophilaApc1 and Apc2 regulate Wingless transduction throughout development
Authors: Ahmed Yashi , Nouri Ali , Wieschaus Eric
Published: April 2021

Inactivation of the Adenomatous Polyposis Coli (APC) tumor suppressor triggers the development of most colorectal carcinomas. APC is required for targeted degradation of β-catenin, the central transcriptional activator in the Wnt/Wingless (Wg) signal transduction pathway; however, the precise biochemical functions of APC remain uncertain. The two Drosophila homologs of APC (Apc1 and Apc2) appear to have predominantly different tissue distributions, different subcellular localizations and mutually exclusive phenotypes upon inactivation. Unexpectedly, we have found that despite these differences, simultaneous reduction in both Drosophila Apc proteins results in the global nuclear accumulation of β-catenin and the constitutive activation of Wg transduction throughout development. This redundancy extends even to functions previously thought to be specific to the individual Apc homologs. Together, these results reveal that the combined activity of Apc1 and Apc2 allows a tight regulation of transcriptional activation by β-catenin and suggest that APC proteins are required for the regulation of Wnt transduction in all cells.
Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1β
Authors: Coffinier Catherine , Gresh Lionel , Fiette Laurence , Tronche François , Schütz Günther , Babinet Charles , Pontoglio Marco , Yaniv Moshe , Barra Jacqueline
Published: April 2021

The inactivation of the Hnf1β gene identified an essential role in epithelial differentiation of the visceral endoderm and resulted in early embryonic death. In the present study, we have specifically inactivated this gene in hepatocytes and bile duct cells using the Cre/loxP system. Mutant animals exhibited severe jaundice caused by abnormalities of the gallbladder and intrahepatic bile ducts (IHBD). The paucity of small IHBD was linked to a failure in the organization of duct structures during liver organogenesis, suggesting an essential function of Hnf1b in bile duct morphogenesis. Mutant mice also lacked interlobular arteries. As HNF1β is not expressed in these cells, it further emphasizes the link between arterial and biliary formation. Hepatocyte metabolism was also affected and we identified hepatocyte-specific HNF1β target genes involved in bile acids sensing and in fatty acid oxidation.
Residues SFQ (173-175) in the large extracellular loop of CD9 are required for gamete fusion
Authors: Zhu Guo-Zhang , Miller Brent J. , Boucheix Claude , Rubinstein Eric , Liu Christopher C. , Hynes Richard O. , Myles Diana G. , Primakoff Paul
Published: April 2021

Gamete fusion is the fundamental first step initiating development of a new organism. Female mice with a gene knockout for the tetraspanin CD9 (CD9 KO mice) produce mature eggs that cannot fuse with sperm. However, nothing is known about how egg surface CD9 functions in the membrane fusion process. We found that constructs including CD9’s large extracellular loop significantly inhibited gamete fusion when incubated with eggs but not when incubated with sperm, suggesting that CD9 acts by interaction with other proteins in the egg membrane. We also found that injecting developing CD9 KO oocytes with CD9 mRNA restored fusion competence to the resulting CD9 KO eggs. Injecting mRNA for either mouse CD9 or human CD9, whose large extracellular loops differ in 18 residues, rescued fusion ability of the injected CD9 KO eggs. However, when the injected mouse CD9 mRNA contained a point mutation (F174 to A) the gamete fusion level was reduced fourfold, and a change of three residues (173-175, SFQ to AAA) abolished CD9’s activity in gamete fusion. These results suggest that SFQ in the CD9 large extracellular loop may be an active site which associates with and regulates the egg fusion machinery.
The electron microscopy and cytochemistry of oogenesis and the cytochemistry of embryonic development of the prosobranch gastropodBembicium nanumL.
Authors: Bedford Lynne
Published: April 2021

Embryonic development in B. nanum is similar to that of Littorina obtusa, apart from differences, especially in the velum and foot, which can be correlated with the planktonic mode of life of the veliger of B. nanum. Electron microscope studies of oogenesis show that fatty yolk formation occurs in association with the vitelline body and with mitochondria, and proteid yolk formation occurs in association with the Golgi apparatus. Nucleo-cytoplas-mic relationships in the growing oocyte are discussed. During oogenesis, cytochemical localizations can be related to the nucleolar activity, elaboration of the endoplasmic reticular elements and the presence of yolk. No preferential distribution of the substances tested occurs in the cytoplasm of the late oocyte. Following fertilization, slight animal-vegetal and radial gradients are established, chiefly in association with the yolk. During cleavage, a definite animal-vegetal gradient is seen in the pattern of cytochemical localizations, but the differences between the cells are only relative, no rigid localizations in one cell or group of cells occurring. During gastrulation, the chemo-differentiation detectable in early embryonic development is well established. The cells of the ectoderm, endoderm and mesoderm are each cytochemically distinct, but no absolute distinctions between each cell type can be shown. During organogenesis, the initial differentiation of both larval and adult cells is accompanied by strongly positive reactions for DNA, RNA and alkaline phosphatase in these cells. Following this initial differentiation, two distinct cell types emerge : (i) Functional larval cells (both ectodermal and endodermal) involved in nutrition and locomotion, showing slight reactions for RNA, DNA and alkaline phosphatase (except where these are involved in cell function) and highly positive reactions for iron, glycogen and PAS-positive material. (ii) Adult rudiment cells, which may be functional in the larva, but are still differentiating towards the adult type and remain strongly positive for DNA, RNA and alkaline phosphatase.
Observations on some tumours found in two species of planaria—Dugesia etrusca and D. ilvana
Authors: Lange C. S.
Published: April 2021

Since the description by Pallas in 1774 of their remarkable capacity for regeneration the planarians have been of interest to the biologist (cf. Brøndsted’s excellent review— Brøndsted, 1955). Dubois (1949) has shown that regeneration in planaria is due to undifferentiated totipotential cells referred to as neoblasts, which are the only cells known to divide mitotically. When the animal is cut or similarly injured, some neoblasts in the region of the wound rapidly differentiate to form a new epidermis, while other neoblasts divide and migrate towards the wound surface where they continue to divide and/or differentiate into various cell types. The finding of spontaneous growths or tumours in this simple material (Goldsmith, 1939) suggests that it may be of interest to study the nature of such tumours.
Formation de cytasters dans les œufs de Batraciens sous l’action de l’eau lourde
Authors: van Assel S. , Brachet J.
Published: April 2021

Des travaux récents de Gross et de ses collaborateurs (Gross & Spindel, 1960 a, b; Gross & Cousineau, 1963; Gross, Spindel & Cousineau, 1963,1964) ont montré que la formation de cytasters, dans le cytoplasme des œufs vierges d’oursins, s’obtient aisément par un traitement avec de l’oxyde de deuterium (eau lourde : D2O). A haute concentration, l’eau lourde agit comme un agent parthéno-génétique.
The morphology and timing of fertilization and early cleavage in the Mongolian gerbil and Deer mouse
Authors: Marston J. H. , Chang M. C.
Published: April 2021

Ovulation, fertilization and early cleavage have been investigated in few myomorph rodents and in only two members of the family Cricetidae. The Golden hamster (subfamily Cricetinae: Mesocricetus auratus) was studied by Graves (1945), Venable (1946a, b), Ward (1948), Strauss (1956) and Harvey, Yanagimachi & Chang (1961), using fixed and stained materials; and Austin (1956a), Samuel & Hamilton (1942) and Hamilton & Samuel (1956) examined the living eggs. The effects of delayed fertilization were investigated by Chang & Fernandez-Cano (1958) and Yanagimachi & Chang (1961). The Field vole (subfamily Microtinae: Microtus agrestis) was studied by Austin (1957).
The effects of erythropoietin on haem synthesis in mouse yolk sac and cultured foetal liver cells
Authors: Cole R. J. , Paul John
Published: April 2021

Erythropoiesis in the foetal mouse is reported to occur initially in the yolk sac, followed by the liver, the spleen and finally the bone marrow (Snell, 1956; Borghese, 1959). At 12 days of gestation 97 % of the circulating erythrocytes are nucleated (Craig & Russell, 1964) and presumably arise from the yolk sac blood islands. The cells of this generation persist in decreasing numbers until the 16th day of gestation. Haemoglobin can first be recognized by histochemical methods (O’Brien, 1961) in the yolk sac before somite formation at the early head fold stage and a network of blood islands, almost covering the embryo, rapidly develops (Plate 1, figs. A–F)’
Developmental effects of chronic maternal audiovisual stress on the rat fetus
Authors: Geber William F.
Published: April 2021

Pregnant Sprague-Dawley albino rats were subjected to controlled audiovisual stress throughout pregnancy. The total effective stress duration amounted to 10 % (6 min) of every hour of the entire day. Total litter resorption occurred in 40 and 50 % of the pregnancies in the young and older females respectively. Litter size was reduced by an average of two fetuses per litter in both age-groups. Visible resorptions per litter were markedly increased in the young females and slightly reduced in the older females. Developmental abnormalities produced included interparietal meningocele, abdominal hernia (omphalocele), spina bifida, and defects of the eye, tail, hind- and forefoot. Hematomas, varying in size and location, were found throughout the cranial area. Localized hematomas were found in the sublingual areas. Osteogenic effects, ranging from partial to complete inhibition, were widespread. There was a marked increase in number and degree of hypo- and hyperdeveloped fetuses over the control rate. Total number of fetuses manifesting some type of developmental deviation amounted to 25 % of the experimental groups and 0-8 % of the control groups. Effects of the audiovisual stress on the maternal organism included slight body-weight loss in both young and older females, decrease in the weight of the adrenals, kidneys, and hearts of the younger females, and increase in organ weight, especially the heart, in the older females. The etiological factors postulated to be responsible for the fetal results are (1) decreased uterine and fetal organ blood flow, and (2) imbalance of the maternal autonomic neurohormone and hypothalamic-pituitary-adrenal relationships.
Studies on pattern regulation in hydra
Authors: Webster Gerald
Published: April 2021

The factors controlling hypostome formation in hydra have been investigated using transplantation techniques. Two factors have been demonstrated, (a) inhibition of hypostome formation and (b) threshold for inhibition. The presence of a hypostome inhibits the formation of another hypostome. This confirms the results of other workers. Inhibition can act in either a disto-proximal or a proximo-distal direction. The level of inhibition is lower in proximal than in distal regions, i.e. the level or effectiveness of inhibition declines as the distance from the hypostome increases. An axial gradient in level of inhibition is postulated. The difference in behaviour of regions from different axial positions when transplanted to the basal disc, i.e. when subjected to identical inhibiting conditions, indicated that regions have different thresholds for inhibition. Distal regions have higher thresholds than proximal regions; an axial gradient in threshold is postulated. The idea of a threshold for inhibition is a new concept as far as regulation in hydroids is concerned. The interaction between threshold and level of inhibition is believed to control hypostome formation. Polarized regulation of hydra into a distal hypostome and a proximal non-hypostomal region is discussed in terms of these concepts. The results are discussed in relation to those obtained by other workers on other hydroids. Re-interpretation of these results suggests that inhibition and threshold are controlling factors in the regulation of other hydroids.
Acid mucopolysaccharides in the development of the Pacific great skate, Raja binoculata
Authors: Mcconnachie P. R. , Ford P.
Published: April 2021

Histochemical treatments specific for hyaluronic acid, C-S-A/C, C-S-B and heparin were applied to a series of Pacific great skate (Raja binoculata) embryos from cleavage to immediate prehatching stages, in order to characterize histochemically the AMPS present in the embryos and to study the events leading to AMPS localization in the adult. A progression was observed: (a) intracellular neutral polysaccharides in cleavage stages, (b) a combination of extracellular polysaccharides and weakly acidic AMPS (hyaluronic acid) associated with cell processes in neurulating stages, (c) extracellular strongly acidic AMPS (chondroitin sulphates) in later stages, particularly in areas of cartilage development. In neurulating embryos hyaluronic acid appeared in quantity between adjacent tissues, suggestive of some developmental significance for this compound. Hyaluronic acid also appeared after neurulation in close association with developing gut and mesonephros. Histochemical localization of these compounds in immediate prehatching stages agreed with previously reported biochemical analyses of shark skin and cartilage, i.e. C-S-B occurred in skin and C-S-A/C was a major component of cartilage matrix.
The relationship of chemical structure to teratogenic activity among bisazo dyes: a re-evaluation
Authors: Lloyd J. B. , Beck F.
Published: April 2021

Samples of five bisazo dyes, trypan blue, Niagara blue 2B, Niagara blue 4B, Afridol blue and Evans blue, of confirmed identity and known purity, have been tested as teratogens by suebutaneous injection into the Wistar rat. Each dye except Niagara blue 4B, if administered at an appropriate dose and stage of pregnancy, shows high activity. Niagara blue 4B at low dose produces a few malformed survivors at term, but in higher doses leads to considerable maternal and embryonic mortality. Serum dye concentrations at intervals after subcutaneous injection were calculated and it was found that when injected at doses which gave maximum teratogenic response serum levels of the same order over the susceptible period were maintained for each dye. The hypothesis is advanced that the observed differences in teratogenic behaviour of the dyes to some extent reflect differences in the handling of the dyes by the mother rather than absolute differences in activity.
On the pars distalis hormone activities involved in spleen development in chicken embryos
Authors: Hart D. E. , Betz T. W.
Published: April 2021

Spleen development was studied in 11 groups of chicken embryos: (1) intact, I; (2) ‘hypo-physectomized H, by partial decapitation, and nine groups of ‘hypophysectomized’ embryos in which each host received a specific type of pars distalis graft; (3) one cephalic region, HCe; (4) one middle region, HM;, (5) one caudal region, HCa;, (6) the entire pars distalis, HE; (7) two cephalic regions, H2Ce; (8) two middle regions, H2M;, (9) two caudal regions, H2Ccr; (10) one cephalic and one caudal region, HCeCcr. or (11) one cephalic, one middle and one caudal region, HCeMCa. Embryos were killed at 20-5 days of incubation. Levels of spleen development were assessed by changes in mean weight and histogenesis.

Spleen development in ‘hypophysectomized’ embryos was normal only with cephalic and middle region pars distalis grafts but not with caudal grafts. Grafts of entire partes distales or of two cephalic regions were no more effective than single cephalic regions in correcting development. Double caudal region grafts were as ineffective as single caudal region grafts. Apparently there are qualitative differences between pars distalis regions. Cephalic and middle grafts probably produced sufficient ACTH and TSH activities to stimulate adequate levels of adrenocorticoids and thyroid hormone and perhaps prolactin to repair spleen development. These may be the only hormones important for spleen development, because caudal graft ineffectiveness suggests that STH is unnecessary and may not be involved.
Cytodynamics and ontogeny of the immune reponse ofXenopus laevisagainst sheep erythrocytes
Authors: Kidder Gerald M. , Ruben Laurens N. , Stevens Jean M.
Published: April 2021

The heterologous red cell response of Xenopus laevis larvae and post-metamorphic toadlets was investigated by means of the immuno-cytoadherence (ICA) technique. Sheep erythrocytes (SRBC) were employed as immunogen.

Toadlets responded to a single injection of immunogen within 4 days, and exhibited a peak level of rosette-forming cells (RFC) in their spleens at 8 days post-injection. Toadlets immunized against sheep erythrocytes gave only a very slight response when tested against rat erythrocytes. A secondary response, much greater in magnitude than the primary re-sponse, wasevident within 2days when previously immunized toadlets were reinjected with the same immunogen. It was concluded that the ICA technique provides a quantitative measure of an acute immune response in these animals.

Larvae which had passed through stage 50 of Nieuwkoop & Faber exhibited substantial increases in RFC in the spleens when tested 6-10 days after injection with sheep erythrocytes. Significantly increased frequencies of RFC in thymi were also noted in these larvae, but the numbers involved were very low and varied considerably. Histological observations of these larvae revealed lymphoid maturation of the spleens and thymi to be essentially complete.

Larvae which had not reached stage 50 according to external morphological criteria, but whose lymphoid organs had matured to a degree equivalent to stage 50, also exhibited strong anti-SRBC response in the spleens. Response in the thymi was low and not statistically significant. Larvae injected at a stage when lymphocytic differentiation was complete in the thymi but had not begun in the spleens did not exhibit an elevated splenic RFC frequency when tested after the spleens had matured. These data suggest that the heterologous red cell response in the larval spleen is dependent upon antigenic challenge to spleens which have reached the stage 50 equivalent in their histogenesis.
Nuclear transplantation with melanophores, ciliated epidermal cells, and the established cell-line A-8 inXenopus laevis
Authors: Kobel H. R. , Brun R. B. , Fischberg M.
Published: April 2021

The developmental potencies of melanophores, ciliated epidermal cells and cells from an established line were tested by means of nuclear transplantation into enucleated Xenopus eggs. Donor nuclei from ciliated epidermal cells of hatching tadpoles never gave rise, after transplantation, to development beyond the blastula stage; nuclei from non-ciliated cells of the same larvae, on the other hand, could fully replace a zygote nucleus. Melanophore nuclei taken from the tailfin of advanced larvae (stage 56) gave rise to blastulae and, in one case, an incipient invagination was observed. Melanophore nuclei taken from tissue cultures, set up from hatching tadpoles, proved to be competent for leading development as far as the heartbeat stage, (stage 33/34), the embryo showing well-elaborated eye Anlagen, muscles, notochord, cement gland, etc. Nuclei from the highly aneuploid established cell-line A-8 were able to give rise to hatching-stage embryos. These results suggest that some condition, provided by culturing, influences the differentiated state so as to improve the chances of the donor nucleus co-operating with the egg’s developmental programme. The important change might be the state of proliferation attained in cultured cells.
Etude des duplications encéphaliques chez l’embryon de Poulet par implantation de mésoderme ventral présomptif
Authors: Vein D.
Published: April 2021

Study of the encephalic duplications produced in the chick embryo by implantation of presumptive ventral mesoderm in the node area

Material from the posterior third of the primitive streak has been implanted in place of Hensen’s node or in its close vicinity. Implants of embryonic haemopoietic tissues were also used as well as inert material (agar) for controls.

The replacement of Hensen’s node by yet-undifferentiated material (even lateral to the streak) leads to encephalic twinning.

The implantation of the same material in a paraxial location leads to various results extending from normal cephalogenesis to encephalic twinning.

There is no effect from the same material when implanted in front of Hensen’s node or behind it, nor is there an effect from other materials when implanted into the node.

It is concluded that the ventral material leads to twinning owing to its ability to participate in the morphogenetic movements of the neighbouring territories, while modifying them, and to form dorsal structures under their influence.
Sex differentiation of the gonad of fry transplanted into the anterior chamber of the adult eye in the teleost,Oryzias latipes
Authors: Satoh Noriyuki
Published: April 2021

In order to examine whether or not sex differentiation in the medaka, Oryzias latipes, is modified by the physiological level of sex hormones in the adult fish, trunk regions containing the gonads of newly hatched fry were transplanted unilaterally into the anterior chamber of the eyes of adult fish.

The grafts could be classified into two types according to the vascularization. One type of graft developed well ; some of them protruded from the eyes of the host fish. In these grafts the connexion of the blood circulation between the graft and the host was detectable without exception. The other type of graft consisted of those specimens without vascularization. The grafts of this type did not grow in size; this condition seemed to be similar to the so-called in vivo culture in the anterior chamber of the eye in rodents. Most of these grafts, however, degenerated.

Judging from the histology of the gonad in the graft, a genetic male graft in the eye of a fish developed into a testis, regardless of the sexuality of the host. This fact was confirmed by two series of experiments. The gonad of a genetic female fry developed into an ovary if the graft was transplanted into a female fish. On the other hand, the gonad of a genetic female graft transplanted into a male fish failed to develop into an ovary, but formed spermatogenetic cells in a gonad of an abnormal structure.

Therefore, it is highly probable that the reversal of sex differentiation from genetic oogonia into spermatogenetic cells is accomplished by the physiological level of the sex hormones in male fish. On the contrary, the sex reversal of genetic males to females is not induced by the physiological level of female sex hormones.
The relationship between the anterior pituitary gland and the pancreas in tail regeneration of the adult newt
Authors: Vethamany-Globus Swani , Liversage Richard A.
Published: April 2021

Histological examination of the amputated tails of 17 hypophysectomized newts revealed abnormal and extremely retarded regenerates; four of them exhibited total inhibition of regeneration. Thus, under the conditions of hypophysectomy, normal tail regeneration does not ensue in the adult Diemictylus viridescens.

Also, hypophysectomy adversely affects the normal histology of both the endocrine and exocrine parts of the pancreas, as observed by the atrophy of the gland in all hypophysectomized cases. Presumably, the normal function of the gland was altered. This relationship between hypophysectomy and the atrophic pancreas suggests a possible involvement of the pancreas in tail and limb regeneration in the adult newt.
Passage of bovine serum albumin from the mother to rabbit blastocysts I. Passage from the circulation to uterine lumen
Authors: Crutchfield Floy L. , Kulangara Abraham C.
Published: April 2021

Dutch belted rabbits were given single intravenous injections of 100 or 200 mg/kg doses of bovine serum albumin (BSA). BSA in serum and uterine fluid at various times after injection was estimated by a quantitative radial immunodiffusion test, which could measure a minimum of 40 ng. The presence of BSA in uterine fluid was confirmed by immuno-electrophoresis and double diffusion in agar.

BSA passes readily into uterine fluid of non-pregnant rabbits, reaching a peak at 12 h after injection, when its concentration is 7–15 % of that in serum. About 72 h seems to be required for equilibration of BSA between serum and uterine fluid, at which time the concentration in the former is about 5 times that in the latter. The kinetics of the process is discussed. Compared to the above, passage of BSA into uterine fluid of pregnant rabbits (5–7 days post coitum) is restricted in the following ways. Significant amounts of BSA appear in the fluid only after a maternal dose of 200 mg/kg. BSA in uterine fluid reaches a peak at 24 h after injection, when it is only 4·5 % of the serum level. The permeability rate seems to decrease with early gestation.

Approximate rates of entry of BSA into uterine lumen of non-pregnant and pregnant rabbits are 0·4 and 0·25 μg/h. BSA seems to be treated like rabbit albumin in its passage across the uterine epithelium. There is no evidence of selection between these proteins.
Embryogenesis of the enteric ganglia in normal mice and in mice that develop congenital aganglionic megacolon
Authors: Webster William
Published: April 2021

Embryological studies on the mouse indicate that, contrary to the classical concept, all the enteric ganglia are from a single, vagal, neural crest source. The immature ganglion cells first enter the gut by way of the newly formed vagal outgrowth at 10 days gestation. The neuroblasts then migrate down the gut in a cranio-caudal direction, being replaced by more neuroblasts from the vagus. By 15 days 12 h the process is complete and ganglion cells are present throughout the gut. The process is continuous and there is no evidence of a lumbosacral origin for any of the intramural ganglia.

In mice which develop aganglionic megacolon the process is basically the same except that the neuroblasts appear to migrate at a slower rate than normal. The result is that the migration of the neuroblasts and the elongation of the gut are out of phase so the migrating neuroblasts cannot reach the end of the gut, despite the fact they migrate 6 – 7 days longer than normal.