bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fgf-8 determines rostral-caudal polarity in the first branchial arch
Authors: Tucker Abigail S. , Yamada Gen , Grigoriou Maria , Pachnis Vassilis , Sharpe Paul T. 
Published: April 2021

ABSTRACT
In mammals, rostral ectomesenchyme cells of the mandibular arch give rise to odontogenic cells, while more caudal cells form the distal skeletal elements of the lower jaw. Signals from the epithelium are required for the development of odontogenic and skeletogenic mesenchyme cells. We show that rostral-caudal polarity is first established in mandibular branchial arch ectomesenchymal cells by a signal, Fgf-8, from the rostral epithelium. All neural crest-derived ectomesenchymal cells are equicompetent to respond to Fgf-8. The restriction into rostral (Lhx-7-expressing) and caudal (Gsc-expressing) domains is achieved by cells responding differently according to their proximity to the source of the signal. Once established, spatial expression domains and cell fates are fixed and maintained by Fgf-8 in conjunction with another epithelial signal, endothelin-1, and by positional changes in ectomesenchymal cell competence to respond to the signal.
Cbfa2 is required for the formation of intra-aortic hematopoietic clusters
Authors: North Trista , Gu Ting-Lei , Stacy Terryl , Wang Qing , Howard Louisa , Binder Michael , Marín-Padilla Miguel , Speck Nancy A. 
Published: April 2021

ABSTRACT
Cbfa2 (AML1) encodes the DNA-binding subunit of a transcription factor in the small family of core-binding factors (CBFs). Cbfa2 is required for the differentiation of all definitive hematopoietic cells, but not for primitive erythropoiesis. Here we show that Cbfa2 is expressed in definitive hematopoietic progenitor cells, and in endothelial cells in sites from which these hematopoietic cells are thought to emerge. Endothelial cells expressing Cbfa2 are in the yolk sac, the vitelline and umbilical arteries, and in the ventral aspect of the dorsal aorta in the aorta/genital ridge/mesonephros (AGM) region. Endothelial cells lining the dorsal aspect of the aorta, and elsewhere in the embryo, do not express Cbfa2. Cbfa2 appears to be required for maintenance of Cbfa2 expression in the endothelium, and for the formation of intra-aortic hematopoietic clusters from the endothelium.
Restriction of developmental potential during divergence of the enteric and sympathetic neuronal lineages
Authors: Pisano Jessica M. , Birren Susan J. 
Published: April 2021

ABSTRACT
In the peripheral nervous system, enteric and sympathetic neurons develop from multipotent neural crest cells. While local environmental signals in the gut and in the region of the sympathetic ganglia play a role in the choice of cell fate, little is known about the mechanisms that underlie restriction to specific neuronal phenotypes. We investigated the divergence and restriction of the enteric and sympathetic neuronal lineages using immuno-isolated neural crest-derived cells from the gut and sympathetic ganglia. Analysis of neuronal and lineage-specific mRNAs and proteins indicated that neural crest-derived cells from the gut and sympathetic ganglia had initiated neuronal differentiation and phenotypic divergence by E14.5 in the rat. We investigated the developmental potential of these cells using expression of tyrosine hydroxylase as a marker for a sympathetic phenotype. Tyrosine hydroxylase expression was examined in neurons that developed from sympathetic and enteric neuroblasts under the following culture conditions: culture alone; coculture with gut monolayers to promote enteric differentiation; or coculture with dorsal aorta monolayers to promote noradrenergic differentiation. Both enteric and sympathetic neuroblasts displayed developmental plasticity at E14.5. Sympathetic neuroblasts downregulated tyrosine hydroxylase in response to signals from the gut environment and enteric neuroblasts increased expression of tyrosine hydroxylase when grown on dorsal aorta or in the absence of other cell types. Tracking of individual sympathetic cells displaying a neuronal morphology at the time of plating indicated that neuroblasts retained phenotypic plasticity even after initial neuronal differentiation had occurred. By E19.5 both enteric and sympathetic neuroblasts had undergone a significant loss of their developmental potential, with most neuroblasts retaining their lineage-specific phenotype in all environments tested. Together our data indicate that the developmental potential of enteric and sympathetic neuroblasts becomes restricted over time and that this restriction takes place not as a consequence of initial neuronal differentiation but during the period of neuronal maturation. Further, we have characterized a default pathway of adrenergic differentiation in the enteric nervous system and have defined a transient requirement for gut-derived factors in the maintenance of the enteric neuronal phenotype.
Responses of plant vascular systems to auxin transport inhibition
Authors: Mattsson Jim , Sung Z. Renee , Berleth Thomas 
Published: April 2021

ABSTRACT
To assess the role of auxin flows in plant vascular patterning, the development of vascular systems under conditions of inhibited auxin transport was analyzed. In Arabidopsis, nearly identical responses evoked by three auxin transport inhibitor substances revealed an enormous plasticity of the vascular pattern and suggest an involvement of auxin flows in determining the sites of vascular differentiation and in promoting vascular tissue continuity. Organs formed under conditions of reduced auxin transport contained increased numbers of vascular strands and cells within those strands were improperly aligned. In leaves, vascular tissues became progressively confined towards the leaf margin as the concentration of auxin transport inhibitor was increased, suggesting that the leaf vascular system depends on inductive signals from the margin of the leaf. Staged application of auxin transport inhibitor demonstrated that primary, secondary and tertiary veins became unresponsive to further modulations of auxin transport at successive stages of early leaf development. Correlation of these stages to anatomical features in early leaf primordia indicated that the pattern of primary and secondary strands becomes fixed at the onset of lamina expansion. Similar alterations in the leaf vascular responses of alyssum, snapdragon and tobacco plants suggest common functions of auxin flows in vascular patterning in dicots, while two types of vascular pattern alterations in Arabidopsis auxin transport mutants suggest that at least two distinct primary defects can result in impaired auxin flow. We discuss these observations with regard to the relative contributions of auxin transport, auxin sensitivity and the cellular organisation of the developing organ on the vascular pattern.
Phases of cytoplasmic and cortical reorganizations of the ascidian zygote between fertilization and first division
Authors: Roegiers Fabrice , Djediat Chakib , Dumollard Ré , Rouviè Christian , Sardet Christian 
Published: April 2021

ABSTRACT
Many eggs undergo reorganizations that localize determinants specifying the developmental axes and the differentiation of various cell types. In ascidians, fertilization triggers spectacular reorganizations that result in the formation and localization of distinct cytoplasmic domains that are inherited by early blastomeres that develop autonomously.
By applying various imaging techniques to the transparent eggs of Phallusia mammillata, we now define 9 events and phases in the reorganization of the surface, cortex and the cytoplasm between fertilization and first cleavage. We show that two of the domains that preexist in the egg (the ER-rich cortical domain and the mitochondria-rich subcortical myoplasm) are localized successively by a microfilament-driven cortical contraction, a microtubule-driven migration and rotation of the sperm aster with respect to the cortex, and finally, a novel microfilament-dependant relaxation of the vegetal cortex. The phases of reorganization we have observed can best be explained in terms of cell cycle-regulated phases of coupling, uncoupling and recoupling of the motions of cortical and subcortical layers (ER-rich cortical domain and mitochondria-rich domain) with respect to the surface of the zygote. At the end of the meiotic cell cycle we can distinguish up to 5 cortical and cytoplasmic domains (including two novel ones; the vegetal body and a yolk-rich domain) layered against the vegetal cortex. We have also analyzed how the myoplasm is partitioned into distinct blastomeres at the 32-cell stage and the effects on development of the ablation of precisely located small fragments.
On the basis of our observations and of the ablation/ transplantation experiments done in the zygotes of Phallusia and several other ascidians, we suggest that the determinants for unequal cleavage, gastrulation and for the differentiation of muscle and endoderm cells may reside in 4 distinct cortical and cytoplasmic domains localized in the egg between fertilization and cleavage.
A role for fasciclin II in the guidance of neuronal migration
Authors: Wright Jay W. , Snyder Mark A. , Schwinof Kristine M. , Combes Stacey , Copenhaver Philip F. 
Published: April 2021

ABSTRACT
The insect cell adhesion receptor fasciclin II is expressed by specific subsets of neural and non-neural cells during embryogenesis and has been shown to control growth cone motility and axonal fasciculation. Here we demonstrate a role for fasciclin II in the guidance of migratory neurons. In the developing enteric nervous system of the moth Manduca sexta, an identified set of neurons (the EP cells) undergoes a stereotyped sequence of migration along the visceral muscle bands of the midgut prior to their differentiation. Probes specific for Manduca fasciclin II show that while the EP cells express fasciclin II throughout embryogenesis, their muscle band pathways express fasciclin II only during the migratory period. Manipulations of fasciclin II in embryonic culture using blocking antibodies, recombinant fasciclin II fragments, and enzymatic removal of glycosyl phosphatidylinositol-linked fasciclin II produced concentration-dependent reductions in the extent of EP cell migration. These results support a novel role for fasciclin II, indicating that this homophilic adhesion molecule is required for the promotion or guidance of neuronal migration.
Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality
Authors: Hamada Yoshio , Kadokawa Yuzo , Okabe Masaru , Ikawa Masahito , Coleman John R. , Tsujimoto Yoshihide 
Published: April 2021

Abstract
Notch family genes encode transmembrane proteins involved in cell-fate determination. Using gene targeting procedures, we disrupted the mouse Notch2 gene by replacing all but one of the ankyrin repeat sequences in the cytoplasmic domain with the E. coli β-galactosidase gene. The mutant Notch2 gene encodes a 380 kDa Notch2-β-gal fusion protein with β-galactosidase activity. Notch2 homozygous mutant mice die prior to embryonic day 11.5, whereas heterozygotes show no apparent abnormalities and are fully viable. Analysis of Notch2 expression patterns, revealed by X-gal staining, demonstrated that the Notch2 gene is expressed in a wide variety of tissues including neuroepithelia, somites, optic vesicles, otic vesicles, and branchial arches, but not heart. Histological studies, including in situ nick end labeling procedures, showed earlier onset and higher incidence of apoptosis in homozygous mutant mice than in heterozygotes or wild type mice. Dying cells were particularly evident in neural tissues, where they were seen as early as embryonic day 9.5 in Notch2-deficient mice. Cells from Notch2 mutant mice attach and grow normally in culture, demonstrating that Notch2 deficiency does not interfere with cell proliferation and that expression of the Notch2-β-gal fusion protein is not toxic per se. In contrast to Notch1-deficient mice, Notch2 mutant mice did not show disorganized somitogenesis, nor did they fail to properly regulate the expression of neurogenic genes such as Hes-5 or Mash1. In situ hybridization studies show no indication of altered Notch1 expression patterns in Notch2 mutant mice. The results indicate that Notch2 plays an essential role in postimplantation development in mice, probably in some aspect of cell specification and/or differentiation, and that the ankyrin repeats are indispensable for its function.
Role ofPax6in development of the cerebellar system
Authors: Engelkamp Dieter , Rashbass Penny , Seawright Anne , Heyningen Veronica van 
Published: April 2021

AbstractPost-mitotic neurons generated at the rhombic lip undertake long distance migration to widely dispersed destinations, giving rise to cerebellar granule cells and the precerebellar nuclei. Here we show that Pax6, a key regulator in CNS and eye development, is strongly expressed in rhombic lip and in cells migrating away from it. Development of some structures derived from these cells is severely affected in Pax6-null Small eye (Pax6Sey/Pax6Sey) embryos. Cell proliferation and initial differentiation seem unaffected, but cell migration and neurite extension are disrupted in mutant embryos. Three of the five precerebellar nuclei fail to form correctly. In the cerebellum the pre-migratory granule cell sub-layer and fissures are absent. Some granule cells are found in ectopic positions in the inferior colliculus which may result from the complete absence of Unc5h3 expression in Pax6Sey/Pax6Sey granule cells. Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3.
Synergistic activities of α3 and α6 integrins are required during apical ectodermal ridge formation and organogenesis in the mouse
Authors: De Arcangelis Adèle , Mark Manuel , Kreidberg Jordan , Sorokin Lydia , Georges-Labouesse Elisabeth 
Published: April 2021

Abstract
Integrins α6β1 and α6β4 are cell surface receptors for laminins. Integrin α6-null mice die at birth with severe skin blistering and defects in the cerebral cortex and in the retina. Integrin α3β1 can associate with laminins and other ligands. Integrin α3-null mice also die at birth, with kidney and lung defects at late stages of development, and moderate skin blistering. To investigate possible overlapping functions between α3 and α6 integrins, we analyzed the phenotype of compound α3−/−/α6−/− mutant embryos. Double homozygous mutant embryos were growth-retarded and displayed several developmental defects not observed in the single mutant animals. First, limb abnormalities characterized by an absence of digit separation and the fusion of preskeletal elements were observed. Further analyses indicated a defect in the apical ectodermal ridge, an essential limb organizing center. In the double mutant, the ridge appeared flattened, and ridge cells did not show a columnar morphology. A strong reduction in ridge cell proliferation and alterations of the basal lamina underlying the ectoderm were observed. These results suggest that α3 and α6 integrins are required for the organization or compaction of presumptive apical ectodermal ridge cells into a distinct differentiated structure. Additional defects were present: an absence of neural tube closure, bilateral lung hypoplasia, and several abnormalities in the urogenital tract. Finally, an aggravation of brain and eye lamination defects was observed. The presence of novel phenotypes in double mutant embryos demonstrates the synergism between α3 and α6 integrins and their essential roles in multiple processes during embryogenesis.
Sonic hedgehog controls epaxial muscle determination through Myf5 activation
Authors: Borycki Anne-Gaëlle , Brunk Brian , Tajbakhsh Shahragim , Buckingham Margaret , Chiang Chin , Emerson Charles P. 
Published: April 2021

ABSTRACT
Sonic hedgehog (Shh), produced by the notochord and floor plate, is proposed to function as an inductive and trophic signal that controls somite and neural tube patterning and differentiation. To investigate Shh functions during somite myogenesis in the mouse embryo, we have analyzed the expression of the myogenic determination genes, Myf5 and MyoD, and other regulatory genes in somites of Shh null embryos and in explants of presomitic mesoderm from wild-type and Myf5 null embryos. Our findings establish that Shh has an essential inductive function in the early activation of the myogenic determination genes, Myf5 and MyoD, in the epaxial somite cells that give rise to the progenitors of the deep back muscles. Shh is not required for the activation of Myf5 and MyoD at any of the other sites of myogenesis in the mouse embryo, including the hypaxial dermomyotomal cells that give rise to the abdominal and body wall muscles, or the myogenic progenitor cells that form the limb and head muscles. Shh also functions in somites to establish and maintain the medio-lateral boundaries of epaxial and hypaxial gene expression. Myf5, and not MyoD, is the target of Shh signaling in the epaxial dermomyotome, as MyoD activation by recombinant Shh protein in presomitic mesoderm explants is defective in Myf5 null embryos. In further support of the inductive function of Shh in epaxial myogenesis, we show that Shh is not essential for the survival or the proliferation of epaxial myogenic progenitors. However, Shh is required specifically for the survival of sclerotomal cells in the ventral somite as well as for the survival of ventral and dorsal neural tube cells. We conclude, therefore, that Shh has multiple functions in the somite, including inductive functions in the activation of Myf5, leading to the determination of epaxial dermomyotomal cells to myogenesis, as well as trophic functions in the maintenance of cell survival in the sclerotome and adjacent neural tube.
Shade avoidance responses are mediated by the ATHB-2 HD-Zip protein, a negative regulator of gene expression
Authors: Steindler Corinna , Matteucci Antonella , Sessa Giovanna , Weimar Thilo , Ohgishi Maki , Aoyama Takashi , Morelli Giorgio , Ruberti Ida 
Published: April 2021

ABSTRACT
The ATHB-2 gene encoding an homeodomain-leucine zipper protein is rapidly and strongly induced by changes in the ratio of red to far-red light which naturally occur during the daytime under the canopy and induce in many plants the shade avoidance response. Here, we show that elevated ATHB-2 levels inhibit cotyledon expansion by restricting cell elongation in the cotyledon-length and-width direction. We also show that elevated ATHB-2 levels enhance longitudinal cell expansion in the hypocotyl. Interestingly, we found that ATHB-2-induced, as well as shade-induced, elongation of the hypocotyl is dependent on the auxin transport system. In the root and hypocotyl, elevated ATHB-2 levels also inhibit specific cell proliferation such as secondary growth of the vascular system and lateral root formation. Consistent with the key role of auxin in these processes, we found that auxin is able to rescue the ATHB-2 lateral root phenotype. We also show that reduced levels of ATHB-2 result in reciprocal phenotypes. Moreover, we demonstrate that ATHB-2 functions as a negative regulator of gene expression in a transient assay. Remarkably, the expression in transgenic plants of a derivative of ATHB-2 with the same DNA binding specificity but opposite regulatory properties results in a shift in the orientation of hypocotyl cell expansion toward radial expansion, and in an increase in hypocotyl secondary cell proliferation. A model of ATHB-2 function in the regulation of shade-induced growth responses is proposed.
Antivin, a novel and divergent member of the TGFβ superfamily, negatively regulates mesoderm induction
Authors: Thisse Christine , Thisse Bernard 
Published: April 2021

ABSTRACT
Mesoderm induction and patterning are mediated by members of the TGFβ superfamily. We have isolated a novel zebrafish member, antivin, that structurally is highly related to mouse lefty. Overexpression of antivin completely abolishes mesoderm induction at blastula stage, yet resultant embryos develop well-patterned epidermal and neural derivatives. The mesoderm-inhibiting activity of antivin can be mimicked by lefty and is suppressed by increasing levels of the mesodermal inducer Activin or its receptors. On the basis of its expression and activity, we propose that Antivin normally functions as a competitive inhibitor of Activin to limit mesoderm induction in the early embryo.
The orderly allocation of mesodermal cells to the extraembryonic structures and the anteroposterior axis during gastrulation of the mouse embryo
Authors: Kinder Simon J. , Tsang Tania E. , Quinlan Gabriel A. , Hadjantonakis Anna-Katerina , Nagy Andras , Tam Patrick P. L. 
Published: April 2021

Abstract
The prospective fate of cells in the primitive streak was examined at early, mid and late stages of mouse gastrula development to determine the order of allocation of primitive streak cells to the mesoderm of the extraembryonic membranes and to the fetal tissues. At the early-streak stage, primitive streak cells contribute predominantly to tissues of the extraembryonic mesoderm as previously found. However, a surprising observation is that the erythropoietic precursors of the yolk sac emerge earlier than the bulk of the vitelline endothelium, which is formed continuously throughout gastrula development. This may suggest that the erythropoietic and the endothelial cell lineages may arise independently of one another. Furthermore, the extraembryonic mesoderm that is localized to the anterior and chorionic side of the yolk sac is recruited ahead of that destined for the posterior and amnionic side. For the mesodermal derivatives in the embryo, those destined for the rostral structures such as heart and forebrain mesoderm ingress through the primitive streak early during a narrow window of development. They are then followed by those for the rest of the cranial mesoderm and lastly the paraxial and lateral mesoderm of the trunk. Results of this study, which represent snapshots of the types of precursor cells in the primitive streak, have provided a better delineation of the timing of allocation of the various mesodermal lineages to specific compartments in the extraembryonic membranes and different locations in the embryonic anteroposterior axis.
Variant Hepatocyte Nuclear Factor 1 is required for visceral endoderm specification
Authors: Barbacci Elena , Reber Michaël , Ott Marie-Odile , Breillat Christelle , Huetz François , Cereghini Silvia 
Published: April 2021

Abstract
Genetic and molecular evidence indicates that visceral endoderm, an extraembryonic cell lineage, is required for gastrulation, early anterior neural patterning, cell death and specification of posterior mesodermal cell fates. We show that variant Hepatocyte Nuclear Factor 1 (vHNF1), a homeodomain-containing transcription factor first expressed in the primitive endoderm, is required for the specification of visceral endoderm. vHnf1-deficient mouse embryos develop normally to the blastocyst stage, start implantation, but die soon afterwards, with abnormal or absent extraembryonic region, poorly organised ectoderm and no discernible visceral or parietal endoderm. However, immunostaining analysis of E5.5 nullizygous mutant embryos revealed the presence of parietal endoderm-like cells lying on an abnormal basal membrane. Homozygous mutant blastocyst outgrowths or differentiated embryonic stem cells do not express early or late visceral endoderm markers. In addition, in vHnf1 null embryoid bodies there is no activation of the transcription factors HNF-4α1, HNF1α and HNF-3γ. Aggregation of vHnf1-deficient embryonic stem cells with wild-type tetraploid embryos, which contribute exclusively to extraembryonic tissues, rescues periimplantation lethality and allows development to progress to early organogenesis. Our results place vHNF1 in a preeminent position in the regulatory network that specifies the visceral endoderm and highlight the importance of this cell lineage for proper growth and differentiation of primitive ectoderm in pregastrulating embryos.