bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling by the TGF-β homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila
Authors: Chen Rui , Halder Georg , Zhang Zhihuan , Mardon Graeme 
Published: April 2021

Abstract
Retinal cell fate determination in Drosophila is controlled by an interactive network of genes, including eyeless, eyes absent, sine oculis and dachshund. We have investigated the role of the TGF-β homolog decapentaplegic in this pathway. We demonstrate that, during eye development, while eyeless transcription does not depend on decapentaplegic activity, the expression of eyes absent, sine oculis and dachshund are greatly reduced in a decapentaplegic mutant background. We also show that decapentaplegic signaling acts synergistically with and at multiple levels of the retinal determination network to induce eyes absent, sine oculis and dachshund expression and ectopic eye formation. These results suggest a mechanism by which a general patterning signal such as Decapentaplegic cooperates reiteratively with tissue-specific factors to determine distinct cell fates during development.
Role of the EGF receptor pathway in growth and patterning of the Drosophila wing through the regulation of vestigial
Authors: Nagaraj Raghavendra , Pickup Amanda T. , Howes Robert , Moses Kevin , Freeman Matthew , Banerjee Utpal 
Published: April 2021

Abstract
Growth and patterning of the Drosophila wing disc depends on the coordinated expression of the key regulatory gene vestigial both in the Dorsal-Ventral (D/V) boundary cells and in the wing pouch. We propose that a short-range signal originating from the core of the D/V boundary cells is responsible for activating EGFR in a zone of organizing cells on the edges of the D/V boundary. Using loss-of-function mutations and ectopic expression studies, we show that EGFR signaling is essential for vestigial transcription in these cells and for making them competent to undergo subsequent vestigial-mediated proliferation within the wing pouch.
HyBra1, a Brachyury homologue, acts during head formation in Hydra
Authors: Technau Ulrich , Bode Hans R. 
Published: April 2021

Abstract
A homologue of the T-box gene, Brachyury, has been isolated from hydra. The gene, termed HyBra1, is expressed in the endoderm and is associated with the formation of the hypostome, the apical part of the head in four different developmental situations. In adults, which are continuously undergoing patterning, HyBra1 is continuously expressed in the hypostome. During budding, hydra’s asexual form of reproduction, the gene is expressed in a small area that will eventually form the hypostome of the developing bud before any morphological sign of budding is apparent. The gene is also expressed very early during head regeneration and is confined to the region that will form the hypostome. During embryogenesis, HyBra1 is expressed shortly before hatching in the region that will form the apical end of the animal, the hypostome. The absence of expression at the apical end of decapitated animals of reg-16, a head formation-deficient mutant, provides additional evidence for a role of HyBra1 during head formation. Further, treatments that alter the head activation gradient have no effect on HyBra1 expression indicating the role of the gene is confined to head formation. Transplantation experiments indicate that the expression occurs before head determination has occurred, but expression does not irreversibly commit tissue to forming a head. A comparison of the function of the Brachyury homologues suggests an evolutionary conservation of a molecular mechanism that has been co-opted for a number of developmental processes throughout evolution.
Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors
Authors: Wu Jun J. , Chen Jing-Xian , Rothman Taube P. , Gershon Michael D. 
Published: April 2021

ABSTRACT
The terminal colon is aganglionic in mice lacking endothelin-3 or its receptor, endothelin B. To analyze the effects of endothelin-3/endothelin B on the differentiation of enteric neurons, E11-13 mouse gut was dissociated, and positive and negative immunoselection with antibodies to p75NTR were used to isolate neural crest- and non-crest-derived cells. mRNA encoding endothelin B was present in both the crest- and non-crest-derived cells, but that encoding preproendothelin-3 was detected only in the non-crest-derived population. The crest- and non-crest-derived cells were exposed in vitro to endothelin-3, IRL 1620 (an endothelin B agonist), and/or BQ 788 (an endothelin B antagonist). Neurons and glia developed only in cultures of crest-derived cells, and did so even when endothelin-3 was absent and BQ 788 was present. Endothelin-3 inhibited neuronal development, an effect that was mimicked by IRL 1620 and blocked by BQ 788. Endothelin-3 failed to stimulate the incorporation of [3H]thymidine or bromodeoxyuridine. Smooth muscle development in non-crest-derived cell cultures was promoted by endothelin-3 and inhibited by BQ 788. In contrast, transcription of laminin α1, a smooth muscle-derived promoter of neuronal development, was inhibited by endothelin-3, but promoted by BQ 788. Neurons did not develop in explants of the terminal bowel of E12 ls/ls (endothelin-3-deficient) mice, but could be induced to do so by endothelin-3 if a source of neural precursors was present. We suggest that endothelin-3/endothelin B normally prevents the premature differentiation of crest-derived precursors migrating to and within the fetal bowel, enabling the precursor population to persist long enough to finish colonizing the bowel.
Requirement of a novel gene, Xin, in cardiac morphogenesis
Authors: Wang Da-Zhi , Reiter Rebecca S. , Lin Jenny Li-Chun , Wang Qin , Williams Haley S. , Krob Sonja L. , Schultheiss Thomas M. , Evans Sylvia , Lin Jim Jung-Ching 
Published: April 2021

ABSTRACT
A novel gene, Xin, from chick (cXin) and mouse (mXin) embryonic hearts, may be required for cardiac morphogenesis and looping. Both cloned cDNAs have a single open reading frame, encoding proteins with 2,562 and 1,677 amino acids for cXin and mXin, respectively. The derived amino acid sequences share 46% similarity. The overall domain structures of the predicted cXin and mXin proteins, including proline-rich regions, 16 amino acid repeats, DNA-binding domains, SH3-binding motifs and nuclear localization signals, are highly conserved. Northern blot analyses detect a single message of 8.9 and 5.8 kilo base (kb) from both cardiac and skeletal muscle of chick and mouse, respectively. In situ hybridization reveals that the cXin gene is specifically expressed in cardiac progenitor cells of chick embryos as early as stage 8, prior to heart tube formation. cXin continues to be expressed in the myocardium of developing hearts. By stage 15, cXin expression is also detected in the myotomes of developing somites. Immunofluorescence microscopy reveals that the mXin protein is colocalized with N-cadherin and connexin-43 in the intercalated discs of adult mouse hearts.
Incubation of stage 6 chick embryos with cXin antisense oligonucleotides results in abnormal cardiac morphogenesis and an alteration of cardiac looping. The myocardium of the affected hearts becomes thickened and tends to form multiple invaginations into the heart cavity. This abnormal cellular process may account in part for the abnormal looping. cXin expression can be induced by bone morphogenetic protein (BMP) in explants of anterior medial mesoendoderm from stage 6 chick embryos, a tissue that is normally non-cardiogenic. This induction occurs following the BMP-mediated induction of two cardiac-restricted transcription factors, Nkx2.5 and MEF2C. Furthermore, either MEF2C or Nkx2.5 can transactivate a luciferase reporter driven by the mXin promoter in mouse fibroblasts. These results suggest that Xin may participate in a BMP-Nkx2.5-MEF2C pathway to control cardiac morphogenesis and looping.
Characterization of an amphioxus paired box gene,AmphiPax2/5/8: developmental expression patterns in optic support cells, nephridium, thyroid-like structures and pharyngeal gill slits, but not in the midbrain-hindbrain boundary region
Authors: Kozmik Zbynek , Holland Nicholas D. , Kalousova Anna , Paces Jan , Schubert Michael , Holland Linda Z. 
Published: April 2021

ABSTRACTOn the basis of developmental gene expression, the vertebrate central nervous system comprises: a forebrain plus anterior midbrain, a midbrain-hindbrain boundary region (MHB) having organizer properties, and a rhombospinal domain. The vertebrate MHB is characterized by position, by organizer properties and by being the early site of action of Wnt1 and engrailed genes, and of genes of the Pax2/5/8 subfamily. Wada and others (Wada, H., Saiga, H., Satoh, N. and Holland, P. W. H. (1998) Development 125, 1113-1122) suggested that ascidian tunicates have a vertebrate-like MHB on the basis of ascidian Pax258 expression there. In another invertebrate chordate, amphioxus, comparable gene expression evidence for a vertebrate-like MHB is lacking. We, therefore, isolated and characterized AmphiPax2/5/8, the sole member of this subfamily in amphioxus. AmphiPax2/5/8 is initially expressed well back in the rhombospinal domain and not where a MHB would be expected. In contrast, most of the other expression domains of AmphiPax2/5/8 correspond to expression domains of vertebrate Pax2, Pax5 and Pax8 in structures that are probably homologous – support cells of the eye, nephridium, thyroid-like structures and pharyngeal gill slits; although AmphiPax2/5/8 is not transcribed in any structures that could be interpreted as homologues of vertebrate otic placodes or otic vesicles. In sum, the developmental expression of AmphiPax2/5/8 indicates that the amphioxus central nervous system lacks a MHB resembling the vertebrate isthmic region. Additional gene expression data for the developing ascidian and amphioxus nervous systems would help determine whether a MHB is a basal chordate character secondarily lost in amphioxus. The alternative is that the MHB is a vertebrate innovation.
Differential transcriptional control as the major molecular event in generating Otx1−/− and Otx2−/− divergent phenotypes
Authors: Acampora Dario , Avantaggiato Virginia , Tuorto Francesca , Barone Paolo , Perera Marzia , Choo Daniel , Wu Doris , Corte Giorgio , Simeone Antonio 
Published: April 2021

Abstract
Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c.) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full- coding cDNA. Interestingly, homozygous mutant mice (hOtx21/hOtx21) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.
The zebrafish bozozok locus encodes Dharma, a homeodomain protein essential for induction of gastrula organizer and dorsoanterior embryonic structures
Authors: Fekany Kimberly , Yamanaka Yojiro , Leung TinChung , Sirotkin Howard I. , Topczewski Jacek , Gates Michael A. , Hibi Masahiko , Renucci Armand , Stemple Derek , Radbill Andy , Schier Alexander F. , Driever Wolfgang , Hirano Toshio , Talbot William S. , Solnica-Krezel Lilianna 
Published: April 2021

Abstract
The dorsal gastrula organizer plays a fundamental role in establishment of the vertebrate axis. We demonstrate that the zebrafish bozozok (boz) locus is required at the blastula stages for formation of the embryonic shield, the equivalent of the gastrula organizer and expression of multiple organizer-specific genes. Furthermore, boz is essential for specification of dorsoanterior embryonic structures, including notochord, prechordal mesendoderm, floor plate and forebrain. We report that boz mutations disrupt the homeobox gene dharma. Overexpression of boz in the extraembryonic yolk syncytial layer of boz mutant embryos is sufficient for normal development of the overlying blastoderm, revealing an involvement of extraembryonic structures in anterior patterning in fish similarly to murine embryos. Epistatic analyses indicate that boz acts downstream of β-catenin and upstream to TGF-β signaling or in a parallel pathway. These studies provide genetic evidence for an essential function of a homeodomain protein in β-catenin-mediated induction of the dorsal gastrula organizer and place boz at the top of a hierarchy of zygotic genes specifying the dorsal midline of a vertebrate embryo.
The Netrin receptor Frazzled is required in the target for establishment of retinal projections in the Drosophila visual system
Authors: Gong Qizhi , Rangarajan Radha , Seeger Mark , Gaul Ulrike 
Published: April 2021

Abstract
Retinal axons in Drosophila make precise topographic connections with their target cells in the optic lobe. Here we investigate the role of the Netrins and their receptor Frazzled in the establishment of retinal projections. We find that the Netrins, although expressed in the target, are not required for retinal projections. Surprisingly, Frazzled, found on both retinal fibers and target cells, is required in the target for attracting retinal fibers, while playing at best a redundant role in the retinal fibers themselves; this finding demonstrates that target attraction is necessary for topographic map formation. Finally, we show that Frazzled is not required for the differentiation of cells in the target. Our data suggest that Frazzled does not function as a Netrin receptor in attracting retinal fibers to the target; nor does it seem to act as a homotypic cell adhesion molecule. We favor the possibility that Frazzled in the target interacts with a component on the surface of retinal fibers, possibly another Netrin receptor.
Spatially regulated SpEts4 transcription factor activity along the sea urchin embryo animal-vegetal axis
Authors: Wei Zheng , Angerer Lynne M. , Angerer Robert C. 
Published: April 2021

Abstract
Because the transcription of the SpHE gene is regulated cell-autonomously and asymmetrically along the maternally determined animal-vegetal axis of the very early sea urchin embryo, its regulators provide an excellent entry point for investigating the mechanism(s) that establishes this initial polarity. Previous studies support a model in which spatial regulation of SpHE transcription relies on multiple nonvegetal positive transcription factor activities (Wei, Z., Angerer, L. M. and Angerer, R. C. (1997) Dev. Biol. 187, 71-78) and a yeast one-hybrid screen has identified one, SpEts4, which binds with high specificity to a cis element in the SpHE regulatory region and confers positive activation of SpHE promoter transgenes (Wei, Z., Angerer, R. C. and Angerer, L. M. (1999) Mol. Cell. Biol. 19, 1271-1278). Here we demonstrate that SpEts4 can bind to the regulatory region of the endogenous SpHE gene because a dominant repressor, created by fusing SpEts4 DNA binding and Drosophila engrailed repression domains, suppresses its transcription. The pattern of expression of the SpEts4 gene is consistent with a role in regulating SpHE transcription in the nonvegetal region of the embryo during late cleavage/early blastula stages. Although maternal transcripts are uniformly distributed in the egg and early cleaving embryo, they rapidly turn over and are replaced by zygotic transcripts that accumulate in a pattern congruent with SpHE transcription. In addition, in vivo functional tests show that the SpEts4 cis element confers nonvegetal transcription of a β-galactosidase reporter gene containing the SpHE basal promoter, and provide strong evidence that the activity of this transcription factor is an integral component of the nonvegetal transcriptional regulatory apparatus, which is proximal to, or part of, the mechanism that establishes the animal-vegetal axis of the sea urchin embryo.
GoosecoidandMix.1repressBrachyuryexpression and are required for head formation inXenopus
Authors: Latinkić B. V. , Smith J. C. 
Published: April 2021

AbstractThe Xenopus homologue of Brachyury, Xbra, is expressed in the presumptive mesoderm of the early gastrula. Induction of Xbra in animal pole tissue by activin occurs only in a narrow window of activin concentrations; if the level of inducer is too high, or too low, the gene is not expressed. Previously, we have suggested that the suppression of Xbra by high concentrations of activin is due to the action of genes such as goosecoid and Mix.1. Here, we examine the roles played by goosecoid and Mix.1 during normal development, first in the control of Xbra expression and then in the formation of the mesendoderm. Consistent with the model outlined above, inhibition of the function of either gene product leads to transient ectopic expression of Xbra. Such embryos later develop dorsoanterior defects and, in the case of interference with Mix.1, additional defects in heart and gut formation. Goosecoid, a transcriptional repressor, appears to act directly on transcription of Xbra. In contrast, Mix.1, which functions as a transcriptional activator, may act on Xbra indirectly, in part through activation of goosecoid.
A novel ontogenetic pathway in hybrid embryos between species with different modes of development
Authors: Raff Elizabeth C. , Popodi Ellen M. , Sly Belinda J. , Turner F. Rudolf , Villinski Jeffrey T. , Raff Rudolf A. 
Published: April 2021

Abstract
To investigate the bases for evolutionary changes in developmental mode, we fertilized eggs of a direct-developing sea urchin, Heliocidaris erythrogramma, with sperm from a closely related species, H. tuberculata, that undergoes indirect development via a feeding larva. The resulting hybrids completed development to form juvenile adult sea urchins. Hybrids exhibited restoration of feeding larval structures and paternal gene expression that have been lost in the evolution of the direct-developing maternal species. However, the developmental outcome of the hybrids was not a simple reversion to the paternal pluteus larval form. An unexpected result was that the ontogeny of the hybrids was distinct from either parental species. Early hybrid larvae exhibited a novel morphology similar to that of the dipleurula-type larva typical of other classes of echinoderms and considered to represent the ancestral echinoderm larval form. In the hybrid developmental program, therefore, both recent and ancient ancestral features were restored. That is, the hybrids exhibited features of the pluteus larval form that is present in both the paternal species and in the immediate common ancestor of the two species, but they also exhibited general developmental features of very distantly related echinoderms. Thus in the hybrids, the interaction of two genomes that normally encode two disparate developmental modes produces a novel but harmonious ontongeny.
Identification and characterization of hydra metalloproteinase 2 (HMP2): a meprin-like astacin metalloproteinase that functions in foot morphogenesis
Authors: Yan Li , Fei Kaiyin , Zhang Jinsong , Dexter Sharon , Sarras Michael P. 
Published: April 2021

ABSTRACT
Several members of the newly emerging astacin metalloproteinase family have been shown to function in a variety of biological events, including cell differentiation and morphogenesis during both embryonic development and adult tissue differentiation. We have characterized a new astacin proteinase, hydra metalloproteinase 2 (HMP2) from the Cnidarian, Hydra vulgaris. HMP2 is translated from a single mRNA of 1.7 kb that contains a 1488 bp open reading frame encoding a putative protein product of 496 amino acids. The overall structure of HMP2 most closely resembles that of meprins, a subgroup of astacin metalloproteinases. The presence of a transient signal peptide and a putative prosequence indicates that HMP2 is a secreted protein that requires post-translational processing. The mature HMP2 starts with an astacin proteinase domain that contains a zinc binding motif characteristic of the astacin family. Its COOH terminus is composed of two potential protein-protein interaction domains: an “MAM” domain (named after meprins, A-5 protein and receptor protein tyrosine phosphatase μ) that is only present in meprin-like astacin proteinases; and a unique C-terminal domain (TH domain) that is also present in another hydra metalloproteinase, HMP1, in Podocoryne metalloproteinase 1 (PMP1) of jellyfish and in toxins of sea anemone. The spatial expression pattern of HMP2 was determined by both mRNA whole-mount in situ hybridization and immunofluorescence studies. Both morphological techniques indicated that HMP2 is expressed only by the cells in the endodermal layer of the body column of hydra. While the highest level of HMP2 mRNA expression was observed at the junction between the body column and the foot process, immunofluorescence studies indicated that HMP2 protein was present as far apically as the base of the tentacles. In situ analysis also indicated expression of HMP2 during regeneration of the foot process. To test whether the higher levels of HMP2 mRNA expression at the basal pole related to processes underlying foot morphogenesis, antisense studies were conducted. Using a specialized technique named localized electroporation (LEP), antisense constructs to HMP2 were locally introduced into the endodermal layer of cells at the basal pole of polyps and foot regeneration was initiated and monitored. Treatment with antisense to HMP2 inhibited foot regeneration as compared to mismatch and sense controls. These functional studies in combination with the fact that HMP2 protein was expressed not only at the junction between the body column and the foot process, but also as far apically as the base of the tentacles, suggest that this meprin-class metalloproteinase may be multifunctional in hydra.