bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of interstitial collagens in cleft formation of mouse embryonic submandibular gland during initial branching
Authors: Fukuda Yuh , Masuda Yukinari , Kishi Jun-Ichi , Hashimoto Yoko , Hayakawa Taro , Nogawa Hiroyuki , Nakanishi Yasuo 
Published: April 2021

Abstract
An interstitial collagenase was purified from the explant medium of bovine dental pulp and was shown to degrade collagens I and III but not IV and V. The enzyme halted cleft initiation in the epithelium of 12day mouse embryonic submandibular glands in vitro, indicating the active involvement of interstitial collagens in the branching morphogenesis. Transmission electron microscopic observation of the intact 12-day gland without any clefts showed the scattered localization of a few collagen fibrils at the epithelial-mesenchymal interface of the bulb and also revealed the presence of numerous microfibrils around the stalk. Collagen bundles were regularly seen close to the wavy basal lamina at the bottom of clefts of the intact 13-day gland and 12-day gland cultured for 17 h under normal conditions. Mesenchymal cells were found in the clefts together with the frequent localization of peripheral nerve fibres and capillary endothelial cells. The collagen bundles were more often observed in the 12-day gland cultured in the presence of bovine dental pulp collagenase inhibitor, which had been shown to enhance cleft formation. In contrast, collagen fibrils were rarely found at the epithelial-mesenchymal interface of the 12-day gland cultured in the presence of Clostridial or bovine dental pulp collagenase. The findings indicated that the formation of interstitial collagen bundles is essential to form clefts in the epithelium both in vivo and in vitro.
Spatial and temporal distribution of the adherens-junction-associated adhesion molecule A-CAM during avian embryogenesis
Authors: Duband Jean-Loup , Volberg Tova , Sabanay Ilana , Thiery Jean Paul , Geiger Benjamin 
Published: April 2021

Abstract
A-CAM (adherens-junction-specific cell adhesion molecule) is a calcium-dependent adhesion molecule which is associated with intercellular adherens junctions in various tissues (Volk & Geiger, 1986, J. Cell Biol. 103. 1441–1450 and 1451–1464). In the present report, we have investigated the distribution of A-CAM during avian morphogenesis by immunofluorescence microscopy and immunoblotting. A-CAM appeared at the onset of gastrulation on developing mesodermal and endodermal cells and was then expressed on tissues derived from the three primary germ layers. During embryonic life, A-CAM was constitutively expressed in a number of tissues including the central and peripheral nervous system, myocardium, muscles, notochord, skin and lens whereas it was found transiently in many tissues ranging from the nephritic tubules and the endoderm of visceral arches to ectodermal placodes. In the adult, in addition to the nervous system, A-CAM was restricted to the skin, lens, heart and testis, and exhibited an apparent molecular weight higher than the one found in the embryo. The prevalence and cell-surface modulation of A-CAM could frequently be correlated with morphogenetic events such as mesenchyme condensation into epithelia or cell clusters (e.g formation of the somitic epithelium, kidney tubules and peripheral ganglia), dissociation of epithelia (e.g. dissociation of the somitic epithelium and segregation of neural crest from the neural tube), separation of cell populations (e.g. fibroblasts and myotubes in the heart) and reorganizations of epithelia (e.g. neurulation). In addition, using electron microscopy, the expression of A-CAM on the surface of aggregating and separating cells could be correlated with the formation and disappearance of adherens junctions. This precisèly scheduled control of A-CAM correlated with early morphogenetic events during embryogenesis suggests that this CAM could play a crucial role in these processes.
Tissue interactions and cell differentiation: neurone-sensory cell interaction during otic development
Authors: Water Thomas R. Van De 
Published: April 2021

ABSTRACT
Statoacoustic ganglion neurones (SAG) are produced by the same group of cells (otic placode) that produce all of the receptor ceils that populate the sensory areas of the inner ear. The observation that ingrowth of SAG neurites to presumptive sensory areas of the inner ear preceded cytodifferentiation of those receptor cells suggested a causal relationship. Results from in vivo, in ovo and in vitro studies do not support a causal relationship. These studies support the hypothesis that the programme for labyrinthine sensory cell differentiation is intrinsic and does not require the extrinsic stimulus of neuronal interaction to trigger its expression. In contrast, developing statoacoustic ganglion neurones appear to require a trophic influence that is supplied by either their peripheral or central target tissues for their survival and maturation in vitro. A mechanism for the ingrowth of SAG dendrites to their appropriate target sites within the inner ear proposes that attractant fields produced by areas of differentiating sensory cells act to guide the nerve growth cones of ingrowing SAG neurites to the appropriate tissues. Preliminary results from a heterochronic series of SAG implants to common age otocysts suggest that these SAG neurones are capable of responding to the attractant fields which are produced by presumptive labyrinthine sensory epithelium over an extended period of otic development. Both in ovo and in vitro studies suggest that spatiotemporal patterns of extracellular matrix molecules may be important components of the attractant fields which are produced by the sensory areas of the developing inner ear and may ultimately result in the specificity of their neuronal connections.
Teratogens and craniofacial malformations: relationships to cell death
Authors: Sulik K. K. , Cook C. S. , Webster W. S. 
Published: April 2021

ABSTRACT
Environmental agents including ethanol, 13-cis retinoic acid (RA, Accutane®), the antimetabolite methotrexate, periods of hypoxia, ionizing radiation or hyperthermic stress, when administered acutely to pregnant experimental animals, induce stagedependent craniofacial malformations comparable to those in corresponding human teratogen syndromes. Acute treatment regimens have allowed analysis of cell populations initially affected and subsequent dysmorphogenetic sequences as well as speculation relative to mechanisms of teratogenesis. In rodent models, ethanol and RA appear to affect similar cell populations and comparable malformations can be induced by both agents. When administered during gastrulation they cause a major insult to the anterior neural plate which results in characteristic ocular, brain and facial malformations comparable to those seen in the fetal alcohol syndrome. Exposure to these drugs at a time just prior to and during neural crest cell migration into the craniofacial and cervical regions results in malformations comparable to those seen in the DiGeorge sequence and/or retinoic acid embryopathy. Slightly later, at the time that the epibranchial placodes are active, insult results in mandibulofacial dysostosislike syndromes. We propose that the pattern of these malformations is related to the particular vulnerability of cells in the vicinity of normal programmed cell death. Cell death is also associated with ionizing radiation and hyperthermia-induced malformations. Both of these teratogens are particularly damaging to the early development of the eye and central nervous system. Teratogenic temperature elevations result in arrest of mitotic activity and death of cells in mitosis. Hypoxia is also associated with cell death in specific regions and subsequent malformation. For example, death of cells in the invaginating olfactory placode has recently been associated with cleft lip formation. The relationship of hypoxia-induced cell death to energy requirements is being explored. Acute treatment with methotrexate results in frontonasal dysplasia (median facial clefts). Combined effects of fluid imbalance, lack of proliferation or death of frontonasal mesenchyme appear to be involved. Although the mechanisms of craniofacial malformation are complex, a common feature for many is excessive cell death for which the embryo may be unable to compensate. Excessive cell death in regions of programmed cell death represents an important, yet little appreciated, mechanism of teratogenesis.
Craniofacial development: a summing up
Authors: Wolpert L. 
Published: April 2021

ABSTRACT
It is convenient to distinguish between three related problems in development: cell differentiation; pattern formation, which is about spatial organization; and morphogenesis in the strict sense, which is about change in form, particularly of cell sheets, but includes cell migration (Wolpert, 1981; Wolpert & Stein, 1984). All these need to be linked to gene action. If one looks forward over the next five to ten years then the future of craniofacial biology lies in molecular cell biology. This is not to say that all the problems at the tissue level have been solved, quite the contrary, but rather that the emphasis must now be at the cell and molecular level.
Craniofacial growth, evolutionary questions
Authors: Gans Carl 
Published: April 2021

ABSTRACT
Understanding the growth of craniofacial systems in mammals, particularly in man, has always posed problems. Such craniofacial systems are formed ontogenetically of multiple tissue types, and the contributions of these tissues do not obviously match the divisions of adult skeletal elements (see Thorogood, this volume). Even the kind and number of segments in the head region continue to attract attention (Maderson, 1987). Furthermore, craniofacial systems appear to show trends toward an unusual number of developmental abnormalities or teratologies. Many of these teratologies suggest that we are not looking at a simple coordinated whole (Salinas, 1982; Shprintzen, 1982); rather, it seems as if multiple cranial and facial components incur differential growth either symmetrically or asymmetrically.
It seems instructive to treat the basis of this curious array of complications from an evolutionary viewpoint, considering two aspects, adaptation and history.
Cellular and molecular aspects of cephalic neural crest development: workshop report
Authors: Bee Jim , Newgreen Don 
Published: April 2021

ABSTRACT
The neural crest (NC) is derived from the ectoderm at the lateral borders of the neural plate and is first distinct during the later stages of neurulation when prospective NC cells segregate from the surrounding epidermal ectoderm and neurectoderm along the entire dorsolateral aspect of the forming and newly formed neural tube. From this origin, NC cells migrate extensive distances throughout the embryo to give rise to a large number of differentiated cell types and contribute to a diverse series of organ systems. This unique cell population therefore poses fundamental questions of the mechanisms underlying morphogenesis and differentiation during embryonic development.
The developmental fate of NC cells reflects their point of origin along the anterior–posterior axis of the embryo. Of particular significance to the present volume is the major contribution of cells derived from the cephalic NC to the facial skeleton.
Mesoderm induction in Xenopus laevis. responding cells must be in contact for mesoderm formation but suppression of epidermal differentiation can occur in single cells
Authors: Symes K. , Yaqoob M. , Smith J. C. 
Published: April 2021

Abstract
When Xenopus embryos are cultured in calcium- and magnesium-free medium (CMFM), the blastomeres lose adhesion but continue dividing to form a loose heap of cells. If divalent cations are restored at the early gastrula stage the cells re-adhere and eventually form muscle (a mesodermal cell type) as well as epidermis. If, however, the cells are dispersed during culture in CMFM, muscle does not form following reaggregation although epidermis does. This suggests that culturing blastomeres in a heap allows the transmission of mesoderm-induction signals from cell to cell while dispersion effectively dilutes the signal.
In this paper, we have attempted to substitute for cell proximity by culturing dispersed blastomeres in XTC mesoderm-inducing factor (MIF). We find that dispersed cells do not respond to XTC-MIF by forming mesodermal cell types after reaggregation, but the factor does inhibit epidermal differentiation. One interpretation of this observation is that an early stage in mesoderm induction is the suppression of epidermal differentiation and that formation of mesoderm may require contact-mediated signals that are produced in response to XTC-MIF.
We have gone on to study the suppression of epidermal differentiation in more detail. We find that this is a dose-dependent phenomenon that can occur in single cells in the absence of cell division. Animal pole blastomeres become more difficult to divert from epidermal differentiation at later stages of development and by stage 12 they are ‘determined’ to this fate. Fibroblast growth factor (FGF) also suppresses epidermal differentiation in isolated animal pole blastomeres and transforming growth factor-β l acts synergistically with FGF in doing so.
Segmentation in leech development
Authors: Weisblat David A. , Price David J. , Wedeen Cathy J. 
Published: April 2021

ABSTRACT
Segments in glossiphoniid leeches, such as Helobdella triserialis, are the products of stereotyped cell lineages that yield identifiable cells from first cleavage. Cell lines generating segmental tissues are separated from those generating prostomial tissues early in development. Segments arise from five bilateral pairs of longitudinal columns of primary blast cells that are generated by five bilateral pairs of embryonic stem cells called teloblasts. There are four ectodermal cell lines (N, O, P and Q) and one mesodermal cell line (M) on each side of the embryo. In normal development, each cell line generates a segmentally iterated set of identified definitive progeny comprising a mixture of cell types. In the M, O and P cell lines, each blast cell generates one segment’s worth of definitive progeny (segmental complement). But the clones of blast cells in each of these three cell lines interdigitate longitudinally with cells of the adjacent clones from the same line, so that the clone of an individual m, o and p blast cell is distributed across more than one segment. Thus, there is no simple clonal basis for morphologically defined segments. In the N and Q cell lines, two blast cells are required to produce one segmental complement of definitive progeny; in each of these two cell lines, two classes of blast cells (nf and ns, qf and qs) are produced in exact alternation. Primary n and q blast cells are about the same size and are produced at the same rate as blast cells for the o and p bandlets, but the longitudinal extent of their clones is roughly half that of the o and p blast cells’ clones. During division of the blast cells, the n and q bandlets become compressed relative to the o and p bandlets, so that the segmental complements of the different cell lines can come into register. This compression movement is manifest as a movement of n and q bandlets relative to o and p bandlets in the posterior portion of the germinal band. The number of true segments in leech is fixed at 32; the counting mechanism is not known, but several hypotheses have been disproved. Segmentation in annelids and arthropods differs extensively at the cellular level, yet these phyla are presumed to share a common segmented ancestor. One strategy to identify homologous processes in annelid and arthropod segmentation is to compare the patterns of expression of evolutionarily conserved, developmentally important genes. Preliminary observations using a cross-reacting antibody that is thought to recognize a highly conserved region of a Drosophila segmentation gene, engrailed, labels nuclei of some blast cells early in development and, later, some neurones in the differentiating suboesophageal ganglion.
Spatially restricted domains of homeo-gene transcripts in mouse embryos: relation to a segmented body plan
Authors: Gaunt Stephen J. , Sharpe Paul T. , Duboule Denis 
Published: April 2021

ABSTRACT
By use of in situ hybridization experiments, the transcripts of several different mouse homeo-genes (Hox-1.2, -1.3, -1.4, -1.5, -3.1 and -6.1) have been localized in 121-day mouse embryos. In a comparison of these genes on adjacent or nearby embryo sections, it is found that their transcripts occupy domains which are usually different, although overlapping, along the anteroposterior axis of the body. The domains are not limited to single segments (assumed to be represented by single prevertebrae) but they encompass regions of adjacent segments. In addition to the prevertebral column, the transcript domains extend into the central nervous system and at least some of the organs (pharynx, thyroid, trachea, lung, stomach and kidney).
Within the prevertebral column, a striking feature of most of the domains is that the abundance of transcripts rises (anteriorly) and falls (posteriorly) over a distance of several adjacent prevertebrae. For Hox-1.4 and Hox-1.3 the rise is over prevertebrae within the cervical region. For Hox-6.1, Hox-1-2 and Hox-3.1, the rise is over prevertebrae within the thoracic region. For each of the genes examined, transcripts in the central nervous system extend to a more anterior position in the body than transcripts in the prevertebral column. The myelencephalon of the hindbrain contains at least three different anterior boundaries for homeo-gene transcript domains. The positions of these are defined by Hox-1.5 (most anterior), Hox-1.4 and Hox-1.3. Anterior boundaries for Hox-6.1 and Hox-1.2 are apparently located at the Hox-1.3 position. Homeo-gene transcript domains extend into several structures known to be derived, at least in part, from the neural crest. These include the ventral pharynx, thyroid, aortic trunk and, probably, the sympathetic nerve chain and thymus.
For several genes of the Hox-1 cluster, we note a correspondence between the serial arrangement of genes on the chromosome and the arrangement of their transcript domains in the developing embryo. We also note some striking similarities between the transcript domains of different homeo-genes that share the same subfamily (Duboule et al. 1988). These observations, and others, offer possible clues about the molecular mechanisms that might underlie the formation and maintenance of homeo-gene transcript domains.
Murine genes with homology to Drosophila segmentation genes
Authors: Dressler Gregory R. , Deutsch Urban , Balling Rudi , Simon Dominique , Guenet Jean-Louis , Gruss Peter 
Published: April 2021

ABSTRACT
As a potential method to define genes that control vertebrate segmentation processes during embryogenesis, murine genes containing a protein domain homologous to the Drosophila paired box sequence were isolated. The mouse genome contains at least three genes with highly conserved paired box like sequences, termed Pax genes, that are also conserved in other vertebrates. During embryogenesis, the Paxl gene is expressed in ventral sclerotome cells and in the intervertebral disks of the vertebral column. Thus, Paxl clearly shows a segmented pattern of expression. A second gene, Pax2, also is expressed in segmented structures of the intermediate mesoderm and in certain regions of ectoderm derived tissues. The Paxl and Pax2 genes map to chromosomes 2 and 7, respectively. Interestingly, several known mutations that affect vertebral column development map near the Paxl locus.
Gradients and insect segmentation
Authors: French Vernon 
Published: April 2021

ABSTRACT
‘Morphogen’ gradients have long been invoked as a means of specifying spatial patterns of developmental fate, and it has now been demonstrated that they are indeed involved in the early steps of insect segmentation.
In many insects, including Drosophila, ligature and transplantation experiments have shown that the segment pattern develops through interactions between the ends of the egg. These results, plus those from irradiation and centrifugation of chironomid eggs, suggest that specific maternally synthesized RNAs are localized at the ends of the oocyte, and act as sources of opposing anterior and posterior gradients in the early egg.
In Drosophila, different groups of maternal ‘seg mentation’ genes are required for depositing within the oocyte terminal, anterior and posterior spatial cues. Injection of wild-type cytoplasm into mutant eggs which lack the anterior (bicoid) or posterior (oskar) cue suggests that these are normally distributed as gradients from strictly localized sources. It has now been shown directly that bicoid RNA passes into the oocyte from the nurse cells, remains localized in the anterior tip, and is later translated into protein which forms an exponential concentration gradient down the early egg. Genes required for posterior spatial information have not yet been cloned, so a posterior gradient (most likely to consist of nanos product) has yet to be directly demonstrated.
Analysis of zygotic ‘segmentation’ genes has shown that the different segment primordia are not directly specified by small changes in the anterior or (postulated) posterior gradient. It seems likely that the maternal cues specify a few bands of expression of zygotic gap genes such as hunchback, Krüppel and knirps, and that the pattern is then elaborated through interactions between these.
The anterior gradient seems to form by diffusion of bicoid protein, but the posterior signal seems to be capable of reorganization in some injection experiments. This could imply a diffusion/reaction mechan ism, or could result simply from the way in which the terminal, anterior and posterior cues act via gap gene activity. Hence the segment pattern formed after injection (and after irradiation of chironomid eggs) will not always correspond to the gradient profile.
Other types of insect egg develop with no nurse cells or external anterior source of RNA and, in these, there is some evidence of a posterior gradient but not of a similar signal from the anterior end.
It is now clear from the analysis of segmentation in Drosophila that the determinants and gradients in ferred from earlier studies do provide a positional framework within which the segment pattern is gradu ally elaborated. Investigation of segmentation in other eggs will be greatly assisted if the molecular techniques can be transferred from Drosophila.
Modifying expression of the engrailed gene of Drosophila melanogaster
Authors: Poole Stephen J. , Kornberg Thomas B. 
Published: April 2021

ABSTRACT
The engrailed gene is required for segmentation of the Drosophila embryo and is expressed in cells constituting the posterior developmental compartments. In mutant embryos lacking engrailed function, portions of the cuticular pattern in each segment are deleted, resulting in fusion of adjacent denticle bands. Using P-element-mediated transposition, we generated flies that express the engrailed gene under the control of an hsp70 promoter, and found that ectopic, heat-shock-induced, engrailed expression caused pattern defects similar to those in embryos lacking engrailed function. Sensitivity to heat shock was only during the cellular blastoderm and early gastrulation periods. This window of sensitivity corresponds to the time when wildtype engrailed protein localizes into segmentally reiterated stripes and represents only a small portion of the normal period of engrailed gene expression.