bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel neuropeptide, Hym-355, positively regulates neuron differentiation in Hydra
Authors: Takahashi Toshio , Koizumi Osamu , Ariura Yuki , Romanovitch Anna , Bosch Thomas C. G. , Kobayakawa Yoshitaka , Mohri Shiro , Bode Hans R. , Yum Seungshic , Hatta Masayuki , Fujisawa Toshitaka 
Published: April 2021

ABSTRACT
During the course of a systematic screening of peptide signaling molecules in Hydra a novel peptide, Hym-355 (FPQSFLPRG-NH2), was identified. A cDNA encoding the peptide was isolated and characterized. Using both in situ hybridization and immunohistochemistry, Hym-355 was shown to be expressed in neurons and hence is a neuropeptide. The peptide was shown to specifically enhance neuron differentiation throughout the animal by inducing interstitial cells to enter the neuron pathway. Further, co-treatment with a PW peptide, which inhibits neuron differentiation, nullified the effects of both peptides, suggesting that they act in an antagonistic manner. This effect is discussed in terms of a feedback mechanism for maintaining the steady state neuron population in Hydra.
Autoregulation and multiple enhancers control Math1 expression in the developing nervous system
Authors: Helms Amy W. , Abney Andrew L. , Ben-Arie Nissim , Zoghbi Huda Y. , Johnson Jane E. 
Published: April 2021

Abstract
Development of the vertebrate nervous system requires the actions of transcription factors that establish regional domains of gene expression, which results in the generation of diverse neuronal cell types. MATH1, a transcription factor of the bHLH class, is expressed during development of the nervous system in multiple neuronal domains, including the dorsal neural tube, the EGL of the cerebellum and the hair cells of the vestibular and auditory systems. MATH1 is essential for proper development of the granular layer of the cerebellum and the hair cells of the cochlear and vestibular systems, as shown in mice carrying a targeted disruption of Math1. Previously, we showed that 21 kb of sequence flanking the Math1-coding region is sufficient for Math1 expression in transgenic mice. Here we identify two discrete sequences within the 21 kb region that are conserved between mouse and human, and are sufficient for driving a lacZ reporter gene in these domains of Math1 expression in transgenic mice. The two identified enhancers, while dissimilar in sequence, appear to have redundant activities in the different Math1 expression domains except the spinal neural tube. The regulatory mechanisms for each of the diverse Math1 expression domains are tightly linked, as separable regulatory elements for any given domain of Math1 expression were not found, suggesting that a common regulatory mechanism controls these apparently unrelated domains of expression. In addition, we demonstrate a role for autoregulation in controlling the activity of the Math1 enhancer, through an essential E-box consensus binding site.
Different clonal dispersion in the rostral and caudal mouse central nervous system
Authors: Mathis Luc , François Nicolas Jean 
Published: April 2021

ABSTRACT
We have performed a systematic clonal analysis to describe the modes of growth, dispersion and production of cells during the development of the mouse neural system. We have used mice expressing a LaacZ reporter gene under the control of the neuron specific enolase promoter to randomly generate LacZ clones in the central nervous system (CNS). We present evidence for (1) a pool of CNS founder cells that is not regionalized, i.e. give descendants dispersed along the entire A-P axis, (2) an early separation between pools of precursors for the anterior and posterior CNS and (3) distinct modes of production of progenitors in these two domains. More specifically, cell growth and dispersion of the progenitors follow a relatively coherent pattern throughout the anterior CNS, a mode that leads to a progressive regionalization of cell fates. In contrast, cell growth of progenitors of the SC appears to involve self-renewing stem cells that progress caudally during regression of the mode. Therefore, at least part of the area surrounding the node is composed of precursors with self-renewing properties and the development of the trunk is dependent on pools of stem cells regressing from A to P. Taken together with our analysis of the cell growth changes associated with neuromere formation (Mathis, L., Sieur, J., Voiculescu, O., Charnay, P. and Nicolas, J. F. (1999) Development 126, 4095-4106), our results suggest that major transitions in CNS development correspond to changes in cell behavior and may provide a link between morphogenesis and genetic patterning mechanisms (i.e. formation of the body plan).
Netrin 1 acts as an attractive or as a repulsive cue for distinct migrating neurons during the development of the cerebellar system
Authors: Alcántara S. , Ruiz M. , Castro F. De , Soriano E. , Sotelo C. 
Published: April 2021

ABSTRACT
Netrin 1 is a long-range diffusible factor that exerts chemoattractive or chemorepulsive effects on developing axons growing to or away from the neural midline. Here we used tissue explants to study the action of netrin 1 in the migration of several cerebellar and precerebellar cell progenitors. We show that netrin 1 exerts a strong chemoattractive effect on migrating neurons from the embryonic lower rhombic lip at E12-E14, which give rise to precerebellar nuclei. Netrin 1 promotes the exit of postmitotic migrating neurons from the embryonic lower rhombic lip and upregulates the expression of TAG-1 in these neurons. In addition, in the presence of netrin 1, the migrating neurons are not isolated but are associated with thick fascicles of neurites, typical of the neurophilic way of migration. In contrast, the embryonic upper rhombic lip, which contains tangentially migrating granule cell progenitors, did not respond to netrin 1. Finally, in the postnatal cerebellum, netrin 1 repels both the parallel fibres and migrating granule cells growing out from explants taken from the external germinal layer. The developmental patterns of expression in vivo of netrin 1 and its receptors are consistent with the notion that netrin 1 secreted in the midline acts as chemoattractive cue for precerebellar neurons migrating circumferentially along the extramural stream. Similarly, the pattern of expression in the postnatal cerebellum suggests that netrin 1 could regulate the tangential migration of postmitotic premigratory granule cells. Thus, molecular mechanisms considered as primarily involved in axonal guidance appear also to steer neuronal cell migration.
Expression of achaete-scute homologues in discrete proneural clusters on the developing notum of the medfly Ceratitis capitata, suggests a common origin for the stereotyped bristle patterns of higher Diptera
Authors: Wülbeck Corinna , Simpson Pat 
Published: April 2021

ABSTRACT
The stereotyped positioning of sensory bristles in Drosophila has been shown to result from complex spatiotemporal regulation of the proneural achaete-scute genes, that relies on an array of cis-regulatory elements and spatially restricted transcriptional activators such as Pannier. Other species of derived schizophoran Diptera have equally stereotyped, but different, bristle patterns. Divergence of bristle patterns could arise from changes in the expression pattern of proneural genes, resulting from evolution of the cis-regulatory sequences and/or altered expression patterns of transcriptional regulators. Here we describe the isolation of achaete-scute homologues in Ceratitis capitata, a species of acalyptrate Schizophora whose bristle pattern differs slightly from that of Drosophila. At least three genes, scute, lethal of scute and asense have been conserved, thus demonstrating that gene duplication within the achaete-scute complex preceded the separation of the families Drosophilidae and Tephritidae, whose common ancestor goes back more than 100 million years. The expression patterns of these genes provide evidence for conservation of many cis-regulatory elements as well as a common origin for the stereotyped patterns seen on the scutum of many Schizophora. Some aspects of the transcriptional regulation have changed, however, and correlate in the notum with differences in the bristle pattern. The Ceratitis pannier gene was isolated and displays a conserved expression domain in the notum.
A new function of BMP4: dual role for BMP4 in regulation ofSonic hedgehogexpression in the mouse tooth germ
Authors: Zhang Yanding , Zhang Zunyi , Zhao Xiang , Yu Xueyan , Hu Yueping , Geronimo Benedicto , Fromm Sigurd H. , Chen YiPing 
Published: April 2021

ABSTRACTThe murine tooth development is governed by sequential and reciprocal epithelial-mesenchymal interactions. Multiple signaling molecules are expressed in the developing tooth germ and interact each other to mediate the inductive tissue interactions. Among them are Sonic hedgehog (SHH), Bone Morphogenetic Protein-2 (BMP2) and Bone Morphogenetic Protein-4 (BMP4). We have investigated the interactions between these signaling molecules during early tooth development. We found that the expression of Shh and Bmp2 is downregulated at E12.5 and E13.5 in the dental epithelium of the Msx1 mutant tooth germ where Bmp4 expression is significantly reduced in the dental mesenchyme. Inhibition of BMP4 activity by noggin resulted in repression of Shh and Bmp2 in wild-type dental epithelium. When implanted into the dental mesenchyme of Msx1 mutants, beads soaked with BMP4 protein were able to restore the expression of both Shh and Bmp2 in the Msx1 mutant epithelium. These results demonstrated that mesenchymal BMP4 represents one component of the signal acting on the epithelium to maintain Shh and Bmp2 expression. In contrast, BMP4-soaked beads repressed Shh and Bmp2 expression in the wild-type dental epithelium. TUNEL assay indicated that this suppression of gene expression by exogenous BMP4 was not the result of an increase in programmed cell death in the tooth germ. Ectopic expression of human Bmp4 to the dental mesenchyme driven by the mouse Msx1 promoter restored Shh expression in the Msx1 mutant dental epithelium but repressed Shh in the wild-type tooth germ in vivo. We further demonstrated that this regulation of Shh expression by BMP4 is conserved in the mouse developing limb bud. In addition, Shh expression was unaffected in the developing limb buds of the transgenic mice in which a constitutively active Bmpr-IB is ectopically expressed in the forelimb posterior mesenchyme and throughout the hindlimb mesenchyme, suggesting that the repression of Shh expression by BMP4 may not be mediated by BMP receptor-IB. These results provide evidence for a new function of BMP4. BMP4 can act upstream to Shh by regulating Shh expression in mouse developing tooth germ and limb bud. Taken together, our data provide insight into a new regulatory mechanism for Shh expression, and suggest that this BMP4-mediated pathway in Shh regulation may have a general implication in vertebrate organogenesis.
The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry
Authors: Watts Jennifer L. , Morton Diane G. , Bestman Jennifer , Kemphues Kenneth J. 
Published: April 2021

ABSTRACT
During the first cell cycle of Caenorhabditis elegans embryogenesis, asymmetries are established that are essential for determining the subsequent developmental fates of the daughter cells. The maternally expressed par genes are required for establishing this polarity. The products of several of the par genes have been found to be themselves asymmetrically distributed in the first cell cycle. We have identified the par-4 gene of C. elegans, and find that it encodes a putative serine-threonine kinase with similarity to a human kinase associated with Peutz-Jeghers Syndrome, LKB1 (STK11), and a Xenopus egg and embryo kinase, XEEK1. Several strong par-4 mutant alleles are missense mutations that alter conserved residues within the kinase domain, suggesting that kinase activity is essential for PAR-4 function. We find that the PAR-4 protein is present in the gonads, oocytes and early embryos of C. elegans, and is both cytoplasmically and cortically distributed. The cortical distribution begins at the late 1- cell stage, is more pronounced at the 2- and 4-cell stages and is reduced at late stages of embryonic development. We find no asymmetry in the distribution of PAR-4 protein in C. elegans embryos. The distribution of PAR-4 protein in early embryos is unaffected by mutations in the other par genes.
Depolarisation causes reciprocal changes in GFRα-1 and GFRα-2 receptor expression and shifts responsiveness to GDNF and neurturin in developing neurons
Authors: Doxakis Epaminondas , Wyatt Sean , Davies Alun M. 
Published: April 2021

ABSTRACT
GDNF and neurturin are structurally related neurotrophic factors that promote the survival of many different kinds of neurons and influence axonal and dendritic growth and synaptic function. These diverse effects are mediated via multicomponent receptors consisting of the Ret receptor tyrosine kinase plus one of two structurally related GPI- linked receptors, GFRα-1 and GFRα-2. To ascertain how the expression of these receptors is regulated during development, we cultured embryonic neurons under different experimental conditions and used competitive RT/PCR to measure the levels of the mRNAs encoding these receptors. We found that depolarising levels of KCl caused a marked increase in GFRα-1 mRNA and a marked decrease in GFRα-2 mRNA in sympathetic, parasympathetic and sensory neurons. These changes were accompanied by increased responsiveness to GDNF and decreased responsiveness to neurturin, and were inhibited by L-type Ca2+ channel antagonists, suggesting that they were due to elevated intracellular free-Ca2+. There was no consistent effect of depolarising levels of KCl on ret mRNA expression, and neither GDNF nor neurturin significantly affected receptor expression. These results show that depolarisation has marked and opposing actions on the expression of GFRα-1 and GFRα-2, which are translated into corresponding changes in neuronal responsiveness to GDNF and neurturin. This provides evidence for a mechanism of regulating the neurotrophic factor responses of neurons by neural activity that has important implications for structural and functional plasticity in the developing nervous system.
Local, possibly contact-mediated signalling restricted to homotypic neurons controls the regular spacing of cells within the cholinergic arrays in the developing rodent retina
Authors: Galli-Resta Lucia 
Published: April 2021

ABSTRACTIn the vertebrate retina neurons of the same type commonly form non-random arrays, assembled by unknown positional mechanisms during development. Computational models in which no two cells are closer than a minimal distance, simulate many retinal arrays. These findings have important biological implications, since they suggest that cells are determined as neurons of specific types before entering their arrays, and that local, possibly contact-mediated interactions acting exclusively among the elements of an array account for its assembly. This is here verified by combining experimental manipulations in normal and transgenic models with computational analysis for the cholinergic mosaics, the only arrays so far for which the development of spatial ordering is known quantitatively. When generalised, these findings suggest a plan for vertebrate retinal patterning, where homotypic interactions organise retinal arrays first, then local interactions between synaptic partners suffice to establish the topographical connections that support retinal processing.
Persistence of Hunchback in the terminal region of the Drosophila blastoderm embryo impairs anterior development
Authors: Janody Florence , Reischl Joachim , Dostatni Nathalie 
Published: April 2021

ABSTRACT
Anterior terminal development is controlled by several zygotic genes that are positively regulated at the anterior pole of Drosophila blastoderm embryos by the anterior (bicoid) and the terminal (torso) maternal determinants. Most Bicoid target genes, however, are first expressed at syncitial blastoderm as anterior caps, which retract from the anterior pole upon activation of Torso. To better understand the interaction between Bicoid and Torso, a derivative of the Gal4/UAS system was used to selectively express the best characterised Bicoid target gene, hunchback, at the anterior pole when its expression should be repressed by Torso. Persistence of hunchback at the pole mimics most of the torso phenotype and leads to repression at early stages of a labral (cap’n’collar) and two foregut (wingless and hedgehog) determinants that are positively controlled by bicoid and torso. These results uncovered an antagonism between hunchback and bicoid at the anterior pole, whereas the two genes are known to act in concert for most anterior segmented development. They suggest that the repression of hunchback by torso is required to prevent this antagonism and to promote anterior terminal development, depending mostly on bicoid activity.
Fate of the mammalian cardiac neural crest
Authors: Jiang Xiaobing , Rowitch David H. , Soriano Philippe , McMahon Andrew P. , Sucov Henry M. 
Published: April 2021

ABSTRACT
A subpopulation of neural crest termed the cardiac neural crest is required in avian embryos to initiate reorganization of the outflow tract of the developing cardiovascular system. In mammalian embryos, it has not been previously experimentally possible to study the long-term fate of this population, although there is strong inference that a similar population exists and is perturbed in a number of genetic and teratogenic contexts. We have employed a two-component genetic system based on Cre/lox recombination to label indelibly the entire mouse neural crest population at the time of its formation, and to detect it at any time thereafter. Labeled cells are detected throughout gestation and in postnatal stages in major tissues that are known or predicted to be derived from neural crest. Labeling is highly specific and highly efficient. In the region of the heart, neural-crest-derived cells surround the pharyngeal arch arteries from the time of their formation and undergo an altered distribution coincident with the reorganization of these vessels. Labeled cells populate the aorticopulmonary septum and conotruncal cushions prior to and during overt septation of the outflow tract, and surround the thymus and thyroid as these organs form. Neural-crest-derived mesenchymal cells are abundantly distributed in midgestation (E9.5-12.5), and adult derivatives of the third, fourth and sixth pharyngeal arch arteries retain a substantial contribution of labeled cells. However, the population of neural-crest-derived cells that infiltrates the conotruncus and which surrounds the noncardiac pharyngeal organs is either overgrown or selectively eliminated as development proceeds, resulting for these tissues in a modest to marginal contribution in late fetal and postnatal life.
Integration of FGF and TWIST in calvarial bone and suture development
Authors: Rice David P. C. , Åberg Thomas , Chan Yan-Shun , Tang Zequn , J. Kettunen Päivi , Pakarinen Leila , Maxson Robert E. , Thesleff Irma 
Published: April 2021

ABSTRACTMutations in the FGFR1-FGFR3 and TWIST genes are known to cause craniosynostosis, the former by constitutive activation and the latter by haploinsufficiency. Although clinically achieving the same end result, the premature fusion of the calvarial bones, it is not known whether these genes lie in the same or independent pathways during calvarial bone development and later in suture closure. We have previously shown that Fgfr2c is expressed at the osteogenic fronts of the developing calvarial bones and that, when FGF is applied via beads to the osteogenic fronts, suture closure is accelerated (Kim, H.-J., Rice, D. P. C., Kettunen, P. J. and Thesleff, I. (1998)Development 125, 1241-1251). In order to investigate further the role of FGF signalling during mouse calvarial bone and suture development, we have performed detailed expression analysis of the splicing variants of Fgfr1-Fgfr3 and Fgfr4, as well as their potential ligand Fgf2. The IIIc splice variants of Fgfr1-Fgfr3 as well as the IIIb variant of Fgfr2 being expressed by differentiating osteoblasts at the osteogenic fronts (E15). In comparison to Fgf9, Fgf2 showed a more restricted expression pattern being primarily expressed in the sutural mesenchyme between the osteogenic fronts. We also carried out a detailed expression analysis of the helix-loop-helix factors (HLH) Twist and Id1 during calvaria and suture development (E10-P6). Twist and Id1 were expressed by early preosteoblasts, in patterns that overlapped those of the FGF ligands, but as these cells differentiated their expression dramatically decreased. Signalling pathways were further studied in vitro, in E15 mouse calvarial explants. Beads soaked in FGF2 induced Twist and inhibited Bsp, a marker of functioning osteoblasts. Meanwhile, BMP2 upregulated Id1. Id1 is a dominant negative HLH thought to inhibit basic HLH such as Twist. In Drosophila, the FGF receptor FR1 is known to be downstream of Twist. We demonstrated that in Twist+/− mice, FGFR2 protein expression was altered. We propose a model of osteoblast differentiation integrating Twist and FGF in the same pathway, in which FGF acts both at early and late stages. Disruption of this pathway may lead to craniosynostosis.
The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer
Authors: Adams Kirk A. , Maida Jennifer M. , Golden Jeffrey A. , Riddle Robert D. 
Published: April 2021

ABSTRACT
Cells in the caudal mesencephalon and rostral metencephalon become organized by signals emanating from the isthmus organizer (IsO). The IsO is associated with the isthmus, a morphological constriction of the neural tube which eventually defines the mesencephalic/ metencephalic boundary (MMB). Here we report that the transcription factor Lmx1b is expressed and functions in a distinct region of the IsO. Lmx1b expression is maintained by the glycoprotein Fgf8, a signal capable of mediating IsO signaling. Lmx1b, in turn, maintains the expression of the secreted factor Wnt1. Our conclusions are substantiated by the following: (i) Lmx1b mRNA becomes localized to the isthmus immediately after Fgf8 initiation, (ii) Wnt1 expression is localized to the Lmx1b expression domain, but with slightly later kinetics, (iii) Fgf8-soaked beads generate similar domains of expression for Lmx1b and Wnt1 and (iv) retroviral-mediated expression of Lmx1b (Lmx1b/RCAS) maintains Wnt1 expression in the mesencephalon. Ectopic Lmx1b is insufficient to alter the expression of a number of other genes expressed at the IsO, suggesting that it does not generate a new signaling center. Instead, if we allow Lmx1b/RCAS-infected brains to develop longer, we detect changes in mesencephalic morphology. Since both ectopic and endogenous Lmx1b expression occurs in regions of the isthmus undergoing morphological changes, it could normally play a role in this process. Furthermore, a similar phenotype is not observed in Wnt1/RCAS-infected brains, demonstrating that ectopic Wnt1 is insufficient to mediate the effect of ectopic Lmx1b in our assay. Since Wnt1 function has been linked to the proper segregation of mesencephalic and metencephalic cells, we suggest that Lmx1b and Wnt1 normally function in concert to affect IsO morphogenesis.