bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avian neural crest-derived neurogenic precursors undergo apoptosis on the lateral migration pathway
Authors: Wakamatsu Yoshio , Mochii Makoto , Vogel Kristine S. , Weston James A. 
Published: April 2021

ABSTRACT
Neural crest cells of vertebrate embryos disperse on distinct pathways and produce different derivatives in specific embryonic locations. In the trunk of avian embryos, crest-derived cells that initially migrate on the lateral pathway, between epidermal ectoderm and somite, produce melanocytes but no neuronal derivatives. Although we found that melanocyte precursors are specified before they disperse on the lateral pathway, we also observed that a few crest-derived neuronal cells are briefly present on the same pathway. Here, we show that neuronal cells are removed by an episode of apoptosis. These observations suggest that localized environmental factor(s) affect the distribution of fate-restricted crest derivatives and function as a ‘proof-reading mechanism’ to remove ‘ectopic’ crest-derived cells.
A potential role for the OTX2 homeoprotein in creating early ‘highways’ for axon extension in the rostral brain
Authors: Nguyen Ba-Charvet Kim Tuyen , Boxberg Ysander von , Guazzi Stefania , Boncinelli Edoardo , Godement Pierre 
Published: April 2021

ABSTRACT
Brain pattern formation starts with a subdivision of the neuroepithelium through site-specific expression of regulatory genes and, subsequently, the boundaries between presumptive neuromeres may provide a scaffold for early formation of axon tracts. In the mouse forebrain, the transcription factor OTX2 is strongly expressed at several such boundaries. Combining dye tracing and staining for OTX2 protein, we show that a number of early fibre tracts develop within stripes of OTX2 expression. To analyse a putative influence of OTX2 on the expression of molecules involved in neurite growth, we generated several clones of NIH3T3 cells stably expressing OTX2 protein at varying levels. As shown by immunoblotting, Otx2 transfection affects the expression of a variety of cell and substratum adhesion molecules, rendering the cells a favourable substratum in neurite outgrowth assays. Among the molecules upregulated with increasing levels of OTX2 are NCAM, tenascin-C and DSD-1-PG, which also in situ colocalize with zones of OTX2 expression at boundaries. These data suggest that Otx2 might be involved in defining local substrata for axon extension in the forebrain.
Evidence for a frizzled-mediated wnt pathway required for zebrafish dorsal mesoderm formation
Authors: Nasevicius Aidas , Hyatt Tana , Kim Hyon , Guttman Julie , Walsh Erin , Sumanas Saulius , Wang Yanshu , Ekker Stephen C. 
Published: April 2021

ABSTRACT
We have used zebrafish as a model system for the study of vertebrate dorsoventral patterning. We isolated a maternally expressed and dorsal organizer localized member of the frizzled family of wnt receptors. Wild-type and dominant, loss-of-function molecules in misexpression studies demonstrate frizzled function is necessary and sufficient for dorsal mesoderm specification. frizzled activity is antagonized by the action of GSK-3, and we show GSK-3 is also required for zebrafish dorsal mesoderm formation. frizzled cooperatively interacts with the maternally encoded zebrafish wnt8 protein in dorsal mesodermal fate determination. This frizzled -mediated wnt pathway for dorsal mesoderm specification provides the first evidence for the requirement of a wnt-like signal in vertebrate axis determination.
The sacral neural crest contributes neurons and glia to the post-umbilical gut: spatiotemporal analysis of the development of the enteric nervous system
Authors: Burns Alan J. , Douarin Nicole M. Le 
Published: April 2021

ABSTRACT
The majority of the enteric nervous system is derived from vagal neural crest cells (NCC), which migrate to the developing gut, proliferate, form plexuses and differentiate into neurons and glia. However, for some time, controversy has existed as to whether cells from the sacral region of the neural crest also contribute to the enteric nervous system. The aim of this study was to investigate the spatiotemporal migration of vagal and sacral NCC within the developing gut and to determine whether the sacral neural crest contributes neurons and glia to the ENS. We utilised quail-chick chimeric grafting in conjunction with antibody labelling to identify graft-derived cells, neurons and glia. We found that vagal NCC migrated ventrally within the embryo and accumulated in the caudal branchial arches before entering the pharyngeal region and colonising the entire length of the gut in a proximodistal direction. During migration, vagal crest cells followed different pathways depending on the region of the gut being colonised. In the pre-umbilical intestine, NCC were evenly distributed throughout the splanchnopleural mesenchyme while, in the post-umbilical intestine, they occurred adjacent to the serosal epithelium. Behind this migration front, NCC became organised into the presumptive Auerbach’s and Meissner’s plexuses situated on either side of the developing circular muscle layer. The colorectum was found to be colonised in a complex manner. Vagal NCC initially migrated within the submucosa, internal to the circular muscle layer, before migrating outwards, adjacent to blood vessels, towards the myenteric plexus region. In contrast, sacral NCC, which also formed the entire nerve of Remak, were primarily located in the presumptive myenteric plexus region and subsequently migrated inwards towards the submucosal ganglia. Although present throughout the post-umbilical gut, sacral NCC were most numerous in the distal colorectum where they constituted up to 17% of enteric neurons, as identified by double antibody labelling using the quail-cell-specific marker, QCPN and the neuron-specific marker, ANNA-1. Sacral NCC were also immunopositive for the glial-specific antibody, GFAP, thus demonstrating that this region of the neural crest contributes neurons and glia to the enteric nervous system.
Transducing positional information to the Hox genes: critical interaction of cdx gene products with position-sensitive regulatory elements
Authors: Charité Jeroen , de Graaff Wim , Consten Dimitri , Reijnen Mark J. , Korving Jeroen , Deschamps Jacqueline 
Published: April 2021

ABSTRACT
Studies of pattern formation in the vertebrate central nervous system indicate that anteroposterior positional information is generated in the embryo by signalling gradients of an as yet unknown nature. We searched for transcription factors that transduce this information to the Hox genes. Based on the assumption that the activity levels of such factors might vary with position along the anteroposterior axis, we devised an in vivo assay to detect responsiveness of cis-acting sequences to such differentially active factors. We used this assay to analyze a Hoxb8 regulatory element, and detected the most pronounced response in a short stretch of DNA containing a cluster of potential CDX binding sites. We show that differentially expressed DNA binding proteins are present in gastrulating embryos that bind to these sites in vitro, that cdx gene products are among these, and that binding site mutations that abolish binding of these proteins completely destroy the ability of the regulatory element to drive regionally restricted expression in the embryo. Finally, we show that ectopic expression of cdx gene products anteriorizes expression of reporter transgenes driven by this regulatory element, as well as that of the endogenous Hoxb8 gene, in a manner that is consistent with them being essential transducers of positional information. These data suggest that, in contrast to Drosophila Caudal, vertebrate cdx gene products transduce positional information directly to the Hox genes, acting through CDX binding sites in their enhancers. This may represent the ancestral mode of action of caudal homologues, which are involved in anteroposterior patterning in organisms with widely divergent body plans and modes of development.
The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development
Authors: Takahashi Motohisa , Tamura Koji , Büscher Dirk , Masuya Hiroshi , Yonei-Tamura Sayuri , Matsumoto Ken , Naitoh-Matsuo Mayumi , Takeuchi Jun , Ogura Keiko , Shiroishi Toshihiko , Ogura Toshihiko , Izpisúa Belmonte Juan Carlos 
Published: April 2021

ABSTRACT
We have determined that Strong’s Luxoid (lstJ) mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.
The Polycomb-group gene eed is required for normal morphogenetic movements during gastrulation in the mouse embryo
Authors: Faust Cynthia , Lawson Kirstie A. , Schork Nicholas J. , Thiel Bonnie , Magnuson Terry 
Published: April 2021

ABSTRACT
We have characterized an induced mutation, called embryonic ectoderm development or eed, that disrupts A-P patterning of the mouse embryo during gastrulation. Positional cloning of this gene revealed it to be the highly conserved homologue of the Drosophila gene extra sex combs, which is required for maintenance of long-term transcriptional repression of homeotic gene expression. Mouse embryos homozygous for loss-of-function alleles of eed initiate gastrulation but display abnormal mesoderm production. Very little embryonic mesoderm is produced; in contrast, extraembryonic mesoderm is relatively abundant. These observations, along with mRNA in situ hybridization analyses, suggested a defect in the anterior primitive streak, from which much of the embryonic mesoderm of the wild-type embryo is derived. To analyse this defect, we initiated clonal analysis of the pre-streak epiblast in eed mutant embryos, using the lineage tracer horseradish peroxidase (HRP). The results of these studies indicate that epiblast cells ingress through the anterior streak, but the newly formed mesoderm does not migrate anteriorly and is mislocalized to the extraembryonic compartment. Abnormal localization of mesoderm to the extraembryonic region did not appear to be due to a restriction and alteration of distal epiblast cell fate, since the majority of clones produced from regions fated to ingress through the anterior streak were mixed, displaying descendants in both embryonic and extraembryonic derivatives. eed mutant embryos also fail to display proper epiblast expansion, particularly with respect to the A-P axis. Based on patterns of clonal spread and calculated clone doubling times for the epiblast, this does not appear to be due to decreased epiblast growth. Rather, epiblast, which is normally fated to make a substantial contribution to the axial midline, appears to make mesoderm preferentially. The data are discussed in terms of global morphogenetic movements in the mouse gastrula and a disruption of signalling activity in the anterior primitive streak.
Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny
Authors: Jaffredo Thierry , Gautier Rodolphe , Eichmann Anne , Dieterlen-Lièvre Françoise 
Published: April 2021

ABSTRACT
We have investigated the developmental relationship of the hemopoietic and endothelial lineages in the floor of the chicken aorta, a site of hemopoietic progenitor emergence in the embryo proper. We show that, prior to the onset of hemopoiesis, the aortic endothelium uniformly expresses the endothelium-specific membrane receptor VEGF-R2. The onset of hemopoiesis can be determined by detecting the common leukocyte antigen CD45. VEGF-R2 and CD45 are expressed in complementary fashion, namely the hemopoietic cluster-bearing floor of the aorta is CD45+/VEGF-R2−, while the rest of the aortic endothelium is CD45−/VEGF-R2+.
To determine if the hemopoietic clusters are derived from endothelial cells, we tagged the E2 endothelial tree from the inside with low-density lipoproteins (LDL) coupled to DiI. 24 hours later, hemopoietic clusters were labelled by LDL. Since no CD45+ cells were inserted among endothelial cells at the time of vascular labelling, hemopoietic clusters must be concluded to derive from precursors with an endothelial phenotype.
XBF-1, a winged helix transcription factor with dual activity, has a role in positioning neurogenesis in Xenopus competent ectoderm
Authors: Bourguignon Catherine , Li Jian , Papalopulu Nancy 
Published: April 2021

ABSTRACT
Neuronal differentiation in the vertebrate nervous system is temporally and spatially controlled by mechanisms which are largely unknown. Here we investigate the role of XBF-1, an anterior neural plate-specific winged helix transcription factor, in controlling the pattern of neurogenesis in Xenopus ectoderm. We show that, in the anterior neural plate of normal embryos, prospective neurogenesis is positioned at the anterior boundary of the XBF-1 expression domain. By misexpressing XBF-1 in the posterior neural plate we show that a high dose of XBF-1 has a dual effect; it suppresses endogenous neuronal differentiation in high expressing cells and induces ectopic neuronal differentiation in adjacent cells. In contrast, a low dose of XBF-1 does not suppress but instead, expands the domain of neuronal differentiation in the lateral and ventral sides of the embryo. XBF-1 regulates the expression of XSox3, X-ngnr-1, X-Myt-1 and X-Delta-1 suggesting that it acts early in the cascade leading to neuronal differentiation. A fusion of XBF-1 to a strong repressor domain (EnR) mimics most of the XBF-1 effects suggesting that the wild type XBF-1 is a transcriptional repressor. However, fusion of XBF-1 to a strong activation domain (E1A) specifically suppresses neuronal differentiation suggesting that XBF-1 may also work as a transcriptional activator. Based on these findings, we propose that XBF-1 is involved in positioning neuronal differentiation by virtue of its concentration dependent, dual activity, as a suppressor and an activator of neurogenesis.
In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex
Authors: Chen Yu , Struhl Gary 
Published: April 2021

ABSTRACT
During Drosophila development, cells belonging to the posterior compartment of each segment organize growth and patterning by secreting Hedgehog (Hh), a protein which induces a thin strip of adjacent cells in the anterior compartment to express the morphogens Decapentaplegic (Dpp) and Wingless (Wg). Hedgehog is bound and transduced by a receptor complex that includes Smoothened (Smo), a member of the Frizzled (Fz) family of seven-pass transmembrane receptors, as well as the multiple-pass transmembrane protein Patched (Ptc). Ptc is required for the binding of Hh to the complex as well as for the Hh-dependent activation of Smo within the complex. Here, we identify a likely null allele of the smo gene and use it to determine whether Hh is bound by Ptc alone, or by Smo in concert with Ptc. We find that cells devoid of Smo can sequester Hh, but that their ability to do so depends, as in wild-type cells, on the expression of high levels of Ptc protein. These results suggest that Ptc normally binds Hh without any help from Smo and hence favor a mechanism of signal transduction in which Hh binds specifically to Ptc and induces a conformational change leading to the release of latent Smo activity.
Functional dominance among Hox genes: repression dominates activation in the regulation of dpp
Authors: Capovilla Maria , Botas Juan 
Published: April 2021

ABSTRACT
Here we investigate the mechanisms by which Hox genes compete for the control of positional identity. Functional dominance is often observed where different Hox genes are co-expressed, and frequently the more posteriorly expressed Hox gene is the one that prevails, a phenomenon known as posterior prevalence. We use dpp674, a visceral mesoderm-specific enhancer of decapentaplegic (dpp), to investigate functional dominance among Hox genes molecularly. We find that posterior prevalence does not adequately describe the regulation of dpp by Hox genes. Instead, we find that abdominal-A (abd-A) dominates over the more posterior Abdominal-B (Abd-B) and the more anterior Ultrabithorax (Ubx). In the context of the dpp674 enhancer, abd-A functions as a repressor whereas Ubx and Abd-B function as activators. Thus, these results suggest that other cases of Hox competition and functional dominance may also be understood in terms of competition for target gene regulation in which repression dominates over activation.
Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells
Authors: Self Tim , Mahony Mary , Fleming Jane , Walsh James , Brown Steve D. M. , Steel Karen P. 
Published: April 2021

ABSTRACT
The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.
Control of noradrenergic differentiation and Phox2a expression by MASH1 in the central and peripheral nervous system
Authors: Hirsch Marie-Rose , Tiveron Marie-Catherine , Guillemot François , Brunet Jean-François , Goridis Christo 
Published: April 2021

ABSTRACT
Mash1, a mammalian homologue of the Drosophila proneural genes of the achaete-scute complex, is transiently expressed throughout the developing peripheral autonomic nervous system and in subsets of cells in the neural tube. In the mouse, targeted mutation of Mash1 has revealed a role in the development of parts of the autonomic nervous system and of olfactory neurons, but no discernible phenotype in the brain has been reported. Here, we show that the adrenergic and noradrenergic centres of the brain are missing in Mash1 mutant embryos, whereas most other brainstem nuclei are preserved. Indeed, the present data together with the previous results show that, except in cranial sensory ganglia, Mash1 function is essential for the development of all central and peripheral neurons that express noradrenergic traits transiently or permanently. In particular, we show that, in the absence of MASH1, these neurons fail to initiate expression of the noradrenaline biosynthetic enzyme dopamine β-hydroxylase. We had previously shown that all these neurons normally express the homeodomain transcription factor Phox2a, a positive regulator of the dopamine β-hydroxylase gene and that a subset of them depend on it for their survival. We now report that expression of Phox2a is abolished or massively altered in the Mash1−/−mutants, both in the noradrenergic centres of the brain and in peripheral autonomic ganglia. These results suggest that MASH1 controls noradrenergic differentiation at least in part by controlling expression of Phox2a and point to fundamental homologies in the genetic circuits that determine the noradrenergic phenotype in the central and peripheral nervous system.
Differential expression and function of cadherin-6 during renal epithelium development
Authors: Cho Eun Ah , Patterson Larry T. , Brookhiser William T. , Mah Steven , Kintner Chris , Dressler Gregory R. 
Published: April 2021

ABSTRACT
The cadherin gene family encodes calcium-dependent adhesion molecules that promote homophilic interactions among cells. During embryogenesis, differential expression of cadherins can drive morphogenesis by stimulating cell aggregation, defining boundaries between groups of cells and promoting cell migration. In this report, the expression patterns of cadherins were examined by immunocytochemistry and in situ hybridization in the embryonic kidney, during the time when mesenchymal cells are phenotypically converted to epithelium and the pattern of the developing nephrons is established. At the time of mesenchymal induction, cadherin-11 is expressed in the mesenchyme but not in the ureteric bud epithelium, which expresses E-cadherin. The newly formed epithelium of the renal vesicle expresses E-cadherin near the ureteric bud tips and cadherin-6 more distally, suggesting that this primitive epithelium is already patterned with respect to progenitor cell types. In the s-shaped body, the cadherin expression patterns reflect the developmental fate of each region. The proximal tubule progenitors express cadherin- 6, the distal tubule cells express E-cadherin, whereas the glomeruli express P-cadherin. Ultimately, cadherin-6 is down-regulated whereas E-cadherin expression remains in most, if not all, of the tubular epithelium. Antibodies generated against the extracellular domain of cadherin-6 inhibit aggregation of induced mesenchyme and the formation of mesenchyme-derived epithelium but do not disrupt ureteric bud branching in vitro. These data suggest that cadherin-6 function is required for the early aggregation of induced mesenchymal cells and their subsequent conversion to epithelium.
mirror, a Drosophila homeobox gene in the iroquois complex, is required for sensory organ and alula formation
Authors: Kehl Benjamin T. , Cho Kyung-Ok , Choi Kwang-Wook 
Published: April 2021

ABSTRACT
The Drosophila notum, the dorsal body wall of the thorax, is subdivided genetically into longitudinal domains (Calleja, M., Moreno, E., Pelaz, S. and Morata, G. (1996) Science 274, 252-255). Two homeobox genes clustered in the iroquois complex, araucan and caupolican, regulate proneural genes and are required for development of sensory bristles in the lateral notum (Gomez-Skarmeta, J. L., del Corral, R. D., de la Calle-Mustienes, E., Ferres-Marco, D. and Modolell, J. (1996) Cell 85, 95-105). An iroquois-related homeobox gene, mirror, was recently isolated and is localized close to the iroquois complex region (McNeil, H., Yang, C.-H., Brodsky, M., Ungos, J. and Simon, M. A. (1997) Genes and Development 11, 1073-1082; this study). We show that mirror is required for the formation of the alula and a subset of sensory bristles in the lateral domain of the notum. Genetic analysis suggests that mirror and the other iroquois genes interact to form the alula as well as the sensory organs. Based on similarities between mirror and the iroquois genes in their genetic map positions, expression, protein structure and function, mirror is considered a new member of the iroquois complex and is involved in prepatterning sensory precursor cells in the lateral notum.