bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereotyped pathway selection by growth cones of early epiphysial neurons in the embryonic zebrafish
Authors: Wilson Stephen W. , Easter Stephen S. 
Published: April 2021

ABSTRACT
In this report we have examined the development of one of the earliest projections in the embryonic zebrafish brain, that from the epiphysis. Epiphysial axons and growth cones were labelled anterogradely in wholemounted brains, using either the carbocyanine dye, dil, or horseradish peroxidase (HRP). Some embryos were also either stained with anti-acetylated tubulin or HNK-1 antibodies to reveal other axons in the brain, or were secondarily sectioned for light and electron microscopy.
The epiphysial axons have a very specific projection pattern and virtually all axons grow precisely to their target regions without error. The first epiphysial growth cone extends ventrally from the epiphysis into the dorsoventral diencephalic tract at 19 –20 h post-fertilisation (h PF). Several hours later, it turns rostrally to grow alongside axons in the tract of the postoptic commissure. The morphology of the leading growth cone changes in predictable ways at different locations along its pathway and these changes correlate with differences in the local environment that it encounters. In contrast to other published descriptions of other developing systems, the epiphysial growth cone is no more complex either when pioneering a pathway, or when encountering divergent axonal pathways. Indeed, it is most complex (i.e. has the greatest number of processes) when it first starts to follow the tract of the postoptic commissure. The presence and selective retention of filopodia within other axonal pathways suggests that growth cones have access to these pathways but do not select them. These observations support the notion that local guidance cues exist within the early scaffold of brain tracts.
Subsequent epiphysial axons form a tight fascicle within the dorsoventral diencephalic tract, but abruptly defasciculate from each other upon turning rostrally into the tract of the postoptic commissure. Epiphysial growth cones that enter this tract at abnormal locations still turn in the appropriate direction. Therefore, guidance cues are not restricted solely to the normal intersections but may be distributed along the length of the tracts.
The epiphysial growth cones and axons have very characteristic spatial relations to other axons in the tracts of the developing brain. They are restricted to the dorsal region of the tract of the postoptic commissure and the rostral region of the postoptic commissure. At early developmental stages, the epiphysial axons are the only axons within the dorsoventral diencephalic tract and they are located very superficially within the neuroepithelium. At later stages, they are displaced to deeper regions of the neuropil by non-epiphysial axons.
Restrictin: a chick neural extracellular matrix protein involved in cell attachment co-purifies with the cell recognition molecule F11
Authors: G. Rathjen Fritz , Wolff Michael , Chiquet-Ehrismann Ruth 
Published: April 2021

ABSTRACT
We report here the characterization of restrictin, a novel chick neural extracellular matrix glycoprotein associated with the cell recognition molecule F11. hnmunoaffinity chromatography using monoclonal antibody 23-13 directed to restrictin yield a maior relative .molecular mass band at 170×103 animmorWas al and 320 ×103 w“ich are immunologically related to each other. Neural cells attach on immobilized restrictin in a short-term adhesion assay. This adhesion can be blocked specifically by monoclonal or polyclonal antibodies to restrictin but not by antibodies to Fll or by the peptide GRGDSP. Antibodies to restrictin do not interfere with the fasciculation of retinal axons and the isolated restrictin does not stimulate the outgrowth of axons. In the developing nervous system, restrictin is localized in very restricted regions and is found within areas of Fll expression. The timing and pattern of expression of restrictin and its cell attachment activity suggest that it participates in developmental events of the nervous system.
Expression of the mouse anti-Müllerian hormone gene suggests a role in both male and female sexual differentiation
Authors: Münsterberg Andrea , Lovell-Badge Robin 
Published: April 2021

ABSTRACT
We describe here the isolation of cDNA and genomic clones corresponding to the mouse gene encoding anti-Müllerian hormone, and the use of these clones as molecular probes to study AMH gene expression. We constructed a 14.5 days post coitum (dpc) mouse fetal testes library and isolated a cDNA clone using bovine, human and rat partial cDNAs as probes. This clone contained a 1 kb insert, which was confirmed by sequencing to be the mouse homologue of AMH. Probes derived from the mouse cDNA clone were used to screen genomic libraries and a 12 kb DNA fragment containing the complete coding region of mouse AMH was isolated. In situ hybridisation was used to determine the precise timing and localisation of AMH expression in male and female embryos and postnatal testes and ovaries. AMH transcripts were first detected in fetal testes at 12.5 Ape when differences between testes and ovaries first become visible. The signal was specific for the Sertoli cells of the testes. Other fetal tissues or female embryos were negative for AMH transcripts. During male development, AMH expression is shut off postnatally. In the female, the expression of AMH was first detected at day 6 after birth and is restricted to granulosa cells. We have correlated the pattern of AMH expression in both sexes with cellular events occurring in gonadal development and discuss some implications that this may have for its function and regulation.
Influence of paternally imprinted genes on development
Authors: Barton Sheila C. , Ferguson-Smith Anne C. , Fundele Reinald , Surani M. Azim 
Published: April 2021

ABSTRACT
The parental origin of chromosomes is critical for normal development in the mouse because some genes are imprinted resulting in a predetermined preferential expression of one of the alleles. Duplication of the paternal (AG: androgenones) or maternal (GG/PG: gynogenones/parthenogenones) genomes will result in an excess or deficiency of gene dosage with corresponding phenotypic effects. Here, we report on the effects of paternally imprinted genes on development following introduction of the AG inner cell mass into normal blastocysts. There was a striking increase in embryonic growth by up to 50%, and a characteristic change in embryonic shape, partly because of the corresponding increase in length of the anterior –posterior axis. These changes, between el2 –el5, were proportional to the contribution from AG cells to the embryo. However, a contribution of AG cells in excess of 50 % was invariably lethal as development progressed to el5. A limited number of chimeras were capable of full-term development provided there was a relatively low contribution from AG cells. The distribution of AG cells in chimeras was not uniform, especially later in development when there was a disproportionate presence of AG cells in the mesodermally derived tissues. Their contribution was consistently greater in the heart and skeletal muscle, but was considerably lower in the brain. Chimeras detected after birth were either dead or developed severe abnormalities of the skeletal elements, particularly of the ribs which were enlarged, distorted and fused, with greatly increased cartilaginous material with an absence of normal ossification. These phenotypic effects in chimeras are reciprocal to those observed in the presence of GG/PG cells, which resulted in a substantial size reduction approaching 50%. Moreover, the GG/PG cells made a relatively substantial contribution to the brain but rarely contributed to skeletal muscle. These observations suggest that the imprinting of some parental alleles establishes a balance of gene dosage which is required for normal embryonic growth regulation and for the development of some lineages. When this balance is altered by duplication of the parental chromosomes, the cumulative effects of imprinted genes are reflected in the phenotypic traits described here. At least part of the phenotypic effects are likely to be due to the imprinting of genes involved in cell interactions as well as for the short-range autocrine/ paracrine factors.
Angiogenesis during human extraembryonic development involves the spatiotemporal control of PDGF ligand and receptor gene expression
Authors: Holmgren Lars , Glaser Anna , Pfeifer-Ohlsson Susan , Ohlsson Rolf 
Published: April 2021

ABSTRACT
We have examined the role of platelet-derived growth factor (PDGF) ligand and receptor genes in the angiogenic process of the developing human placenta. In situ hybridization analysis of first trimester placentae showed that most microcapillary endothelial cells coexpress the PDGF-B and PDGF β-receptor genes. This observation indicates that PDGF-B may participate in placental angiogenesis by forming autostimulatory loops in capillary endothelial cells to promote cell proliferation. Endothelial cells of macro blood vessels maintained high PDGF-B expression, whereas PDGF β-receptor mRNA was not detectable. In contrast, PDGF β-receptor mRNA was readily detectable in fibroblastlike cells and smooth muscle cells in the surrounding intima of intermediate and macro blood vessels. Taken together, these data suggest that the PDGF-B signalling pathway appears to switch from an autocrine to a paracrine mechanism to stimulate growth of surrounding PDGF β-receptor-positive mesenchymal stromal cells.Smooth muscle cells of the blood vessel intima also expressed the PDGF-A gene, the protein product of which is presumably targeted to the fibroblast-like cells of the mesenchymal stroma as these cells were the only ones expressing the PDGF α-receptor. PDGF-A expression was also detected in columnar cytotrophoblasts where it may have a potential role in stimulating mesenchymal cell growth at the base of the growing placental villi. We discuss the possibility that the regulation of the PDGF-B and β-receptor gene expression might represent the potential targets for primary angiogenic factors.
Origins of the insect enteric nervous system: differentiation of the enteric ganglia from a neurogenic epithelium
Authors: Copenhaver Philip F. , Taghert Paul H. 
Published: April 2021

ABSTRACT
The enteric nervous system (ENS) of the moth Manduca sexta is organized into two distinct cellular domains: an anterior domain that includes several small ganglia on the surface of the foregut, and a more posterior domain consisting of a branching nerve plexus (the enteric plexus) that spans the foregut-midgut boundary. Previously, we showed that the neurons of the posterior domain, the enteric plexus, are generated from a large placode that invaginates from the caudal lip of the foregut; subsequently, the cells become distributed throughout the enteric plexus by a sequence of active migration. We now demonstrate that the neurons of the anterior domain, the cells of the enteric ganglia, arise via a distinct developmental sequence. Shortly after the foregut has begun to form, three neurogenic zones differentiate within the foregut epithelium and give rise to chains of cells that emerge onto the foregut surface. The three zones are not sites of active mitosis, as indicated by the absence of labelling with a thymidine analogue and by clonal analyses using intracellularly injected dyes. Rather, the zones serve as loci through which epithelial cells are recruited into a sequence of delamination and neuronal differentiation. As they emerge from the epithelium, the cells briefly become mitotically active, each cell dividing once or twice. In this manner, they resemble the midline precursor class of neural progenitors in the insect central nervous system more than neuroblast stem cells. The progeny of these zone-derived precursors then gradually coalesce into the ganglia and nerves of the anterior ENS. Although this reorganization results in some variability in the precise configuration of neurons within the ganglia, the overall morphology of the ganglia is highly stereotyped, consisting of cortical layers of cells that surround a ventral neuropil. In addition, a number of the neurons within the frontal and hypocerebral ganglia express identifiable phenotypes in a manner that is similar to many cells of the insect central nervous system. These observations indicate that the differentiation of the enteric ganglia in Manduca involves an unusual combination of features seen during the formation of other regions of the nervous system and, as such, constitutes a distinct program of neurogenesis.
Expression and function of the Drosophila gene runt in early stages of neural development
Authors: Duffy J. B. , Kania M. A. , Gergen J. P. 
Published: April 2021

ABSTRACT
The Drosophila gene runt was initially identified on the basis of its role during segmentation. Recent molecular and genetic studies have demonstrated that the runt gene encodes a novel nuclear protein whose developmental importance is not exclusive to segmentation. This report addresses the functional relevance of runt expression in the developmental pathway of neurogenesis. Antibodies against the runt protein reveal that it is expressed in a subset of neuroblasts, ganglion-mother cells and neurons. A subset of these neurons also co-express the segmentation gene even-skipped (eve). Using eve as a marker, we show that runt is required for the normal development of these neurons. A runt P-transposon that lacks neural eis-regulatory elements is used to show that these neurons require runt activity independent of its activity during segmentation. These results are confirmed using a temperature-sensitive runt allele. Further temperature-shift experiments indicate that the requirement for runt is during an early stage of neurogenesis. Based on its pattern of expression and its temporal requirements, runt is distinguished as one of the earliest acting genes involved in the generation of diverse cell fates in the developing Drosophila nervous system.
hairy gene function in the Drosophila eye: normal expression is dispensable but ectopic expression alters cell fates
Authors: Brown Nadean L. , Sattler Carol A. , Markey Donald R. , Carroll Sean B. 
Published: April 2021

ABSTRACT
The regulatory gene hairy is expressed and required during early embryogenesis to control segmentation gene expression properly and during larval and pupal development to control the pattern of certain adult sensory structures. We have found the hairy protein to be expressed transiently during two stages of eye imaginai disc development, including all cells immediately anterior to the morphogenetic furrow that traverses the developing eye disc, and again in the presumptive R7 photoreceptor cells of the developing ommatidia. This pattern is conserved in a significantly diverged Drosophila species. We show that, surprisingly, ommatidia formed by homozygous hairy- mutant clones are apparently normal, indicating that hairy function in the eye is dispensable. However, we do find that ectopic expression of hairy causes numerous structural abnormalities and the alteration of cell fates. Thus, proper regulation of hairy is still essential for normal eye development. We suggest that the loss of hairy function may be compensated by other regulatory proteins, as has been observed previously for several structurally and functionally related genes involved in sensory organ development. The effects of ectopic hairy expression may result from interactions with proneural genes involved in the development of the eye and other sensory organs.
Pax-6, a murine paired box gene, is expressed in the developing CNS
Authors: Walther Claudia , Gruss Peter 
Published: April 2021

ABSTRACT
A multigene family of paired-box-containing genes (Pax genes) has been identified in the mouse. In this report, we describe the expression pattern of Pax-6 during embryogenesis and the isolation of cDNA clones spanning the entire coding region. The Pax-6 protein consists of 422 amino acids as deduced from the longest open reading frame and contains, in addition to the paired domain, a paired-type homeodomain. Beginning with day 8 of gestation, Pax-6 is expressed in discrete regions of the forebrain and the hindbrain. In the neural tube, expression is mainly confined to mitotic active cells in the ventral ventricular zone along the entire anteroposterior axis starting at day 8.5 of development. Pax-6 is also expressed in the developing eye, the pituitary and the nasal epithelium.
TGFβ1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture
Authors: Godin Isabelle , Wylie C. C. 
Published: April 2021

ABSTRACT
Primordial germ cells are the stem cells that provide the functional gametes of adult animals. In many animal groups they are set aside at the earliest stages of development, and migrate from their sites of first appearance to the sites where the gonad will form, the genital ridges. During this migration they proliferate. In the mouse embryo their numbers increase from less than one hundred to approximately four thousand during the period of their migration. In a previous paper we showed that both the proliferation and the direction of migration of mouse PGCs in culture were influenced by soluble factors released from their target tissue, the genital ridges. Studies on other stem cell populations have shown that complex combinations of growth factors control their proliferation, migration and differentiation. In this paper, we show that TGFβ1 inhibits proliferation of PGCs taken from 8.5 day old embryos and cultured on embryonic fibroblast feeder layers. We also show that the previously reported chemotropic effect of genital ridges in this culture system is mediated by TGFβ1, or a closely related molecule, released from the genital ridges.
Homeobox genes and models for patterning the hindbrain and branchial arches
Authors: Hunt Paul , Whiting Jenny , Muchamore Ian , Marshall Heather , Krumlauf Robb 
Published: April 2021

Abstract
Antennapedia class homeobox genes, which in insects are involved in regional specification of the segmented central regions of the body, have been implicated in a similar role in the vertebrate hindbrain. The development of the hindbrain involves the establishment of compartments which are subsequently made distinct from each other by Hox gene expression, implying that the lineage of neural cells may be an important factor in their development. The hindbrain produces the neural crest that gives rise to the cartilages of the branchial skeleton. Lineage also seems to be important in the neural crest, as experiments have shown that the crest will form cartilages appropriate to its level of origin when grafted to a heterotopic location. We show how the Hox genes could also be involved in patterning the mesenchymal structures of the branchial skeleton.
Recently it has been proposed that the rhombomere-restricted expression pattern of Hox 2 genes is the result of a tight spatially localised induction from underlying head mesoderm, in which a prepattern of Hox expression is visible. We find no evidence for this model, our data being consistent with the idea that the spatially localised expression pattern is a result of segmentation processes whose final stages are intrinsic to the neural plate.
We suggest the following model for patterning in the branchial region. At first a segment-restricted code of Hox gene expression becomes established in the neuroepithelium and adjacent presumptive neural crest. This expression is then maintained in the neural crest during migration, resulting in a Hox code in the cranial ganglia and branchial mesenchyme that reflects the crest’s rhombomere of origin. The final stage is the establishment of Hox 2 expression in the surface ectoderm which is brought into contact with neural crest-derived branchial mesenchyme. The Hox code of the branchial ectoderm is established later in development than that of the neural plate and crest, and involves the same combination of genes as the underlying crest. Experimental observations suggest the idea of an instructive interaction between branchial crest and its overlying ectoderm, which would be consistent with our observations.
The distribution of clusters of Antennapedia class genes within the animal kingdom suggests that the primitive chordates ancestral to vertebrates had at least one Hox cluster. The origin of the vertebrates is thought to have been intimately linked to the appearance of the neural crest, initially in the branchial region. Our data are consistent with the idea that the branchial region of the head arose in evolution before the more anterior parts, the development of the branchial region employing the Hox genes in a more determinate patterning system. In this scenario, the anterior parts of the head arose subsequently, which may explain the greater importance of interactions in their development, and the fact that Antennapedia class Hox genes are not expressed there.
Scarless wound repair: a human fetal skin model
Authors: Lorenz H. Peter , Longaker Michael T. , Perkocha Luke A. , Jennings Russell W. , Harrison Michael R. , Adzick N. Scott 
Published: April 2021

ABSTRACT
Animal studies demonstrate that the fetus heals cutaneous wounds by reformation of normal tissue architecture without scar formation. We have developed a new model to study human fetal skin wound healing. Grafts of human fetal skin placed onto athymie mice retain the morphologic features of normal development, although they differentiate at an accelerated rate when placed cutaneously compared to subcutaneously. Fullthickness skin grafts from human fetuses at 15 (n=12), 17 (n=ll), 18 (n=25), 19 (n=20) and 22 (n=13) weeks gestational age were placed onto athymie (nu/nu) mice in 2 locations: (1) cutaneously onto a fascial bed and thereby exposed to air or (2) subcutaneously in a pocket under the murine panniculus carnosus. Linear incisions were made in each graft 7 days after transplantation. Grafts were harvested at 7, 14 and 21 days postwounding and analyzed histologically for scar formation.
By hematoxylin & eosin and Mallory’s trichrome stains, complete epidermal and dermal graft wound healing without scar formation was demonstrated in the subcutaneous grafts at each gestational age studied. In contrast, scar was seen at all time points in the cutaneous grafts in both the incisional wound and at the interface of the fetal human skin graft and adult mouse skin, regardless of fetal skin gestational age.
Our results demonstrate that: (1) human fetal skin can heal without a scar in a subcutaneous adult environment; (2) scarless repair does not depend upon either perfusion by fetal serum or the unique amniotic fluid intrauterine environment; (3) in contrast to subcutaneous grafts, cutaneous grafts of 15, 17, 18, 19 and 22 week gestation fetal skin heal with scar.