bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of neurogenin3 reveals an islet cell precursor population in the pancreas
Authors: Schwitzgebel Valérie M. , Scheel David W. , Conners Jennifer R. , Kalamaras Julie , Lee Jacqueline E. , Anderson David J. , Sussel Lori , Johnson Jeffrey D. , German Michael S. 
Published: April 2021

ABSTRACT
Differentiation of early gut endoderm cells into the endocrine cells forming the pancreatic islets of Langerhans depends on a cascade of gene activation events controlled by transcription factors including the basic helix-loop-helix (bHLH) proteins. To delineate this cascade, we began by establishing the position of neurogenin3, a bHLH factor found in the pancreas during fetal development. We detect neurogenin3 immunoreactivity transiently in scattered ductal cells in the fetal mouse pancreas, peaking at embryonic day 15.5. Although not detected in cells expressing islet hormones or the islet transcription factors Isl1, Brn4, Pax6 or PDX1, neurogenin3 is detected along with early islet differentiation factors Nkx6.1 and Nkx2.2, establishing that it is expressed in immature cells in the islet lineage. Analysis of transcription factor-deficient mice demonstrates that neurogenin3 expression is not dependent on neuroD1/BETA2, Mash1, Nkx2.2, Nkx6.1, or Pax6. Furthermore, early expression of neurogenin3 under control of the Pdx1 promoter is alone sufficient to drive early and ectopic differentiation of islet cells, a capability shared by the pancreatic bHLH factor, neuroD1/BETA2, but not by the muscle bHLH factor, MyoD. However, the islet cells produced in these transgenic experiments are overwhelmingly α cells, suggesting that factors other than the bHLH factors are required to deviate from a default α cell fate. These data support a model in which neurogenin3 acts upstream of other islet differentiation factors, initiating the differentiation of endocrine cells, but switching off prior to final differentiation. The ability to uniquely identify islet cell precursors by neurogenin3 expression allows us to determine the position of other islet transcription factors in the differentiation cascade and to propose a map for the islet cell differentiation pathway.
dackel acts in the ectoderm of the zebrafish pectoral fin bud to maintain AER signaling
Authors: Grandel Heiner , Draper Bruce W. , Schulte-Merker Stefan 
Published: April 2021

ABSTRACT
Classical embryological studies have implied the existence of an apical ectodermal maintenance factor (AEMF) that sustains signaling from the apical ectodermal ridge (AER) during vertebrate limb development. Recent evidence suggests that AEMF activity is composed of different signals involving both a sonic hedgehog (Shh) signal and a fibroblast growth factor 10 (Fgf10) signal from the mesenchyme. In this study we show that the product of the dackel (dak) gene is one of the components that acts in the epidermis of the zebrafish pectoral fin bud to maintain signaling from the apical fold, which is homologous to the AER of tetrapods. dak acts synergistically with Shh to induce fgf4 and fgf8 expression but independently of Shh in promoting apical fold morphogenesis. The failure of dak mutant fin buds to progress from the initial fin induction phase to the autonomous outgrowth phase causes loss of both AER and Shh activity, and subsequently results in a proximodistal truncation of the fin, similar to the result obtained by ridge ablation experiments in the chicken. Further analysis of the dak mutant phenotype indicates that the activity of the transcription factor engrailed 1 (En1) in the ventral non-ridge ectoderm also depends on a maintenance signal probably provided by the ridge. This result uncovers a new interaction between the AER and the dorsoventral organizer in the zebrafish pectoral fin bud.
Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation
Authors: Koyano-Nakagawa Naoko , Kim Jaesang , Anderson David , Kintner Chris 
Published: April 2021

ABSTRACT
During the development of the vertebrate nervous system, neurogenesis is promoted by proneural bHLH proteins such as the neurogenins, which act as potent transcriptional activators of neuronal differentiation genes. The pattern by which these proteins promote neuronal differentiation is thought to be governed by inhibitors, including a class of transcriptional repressors called the WRPW-bHLH proteins, which are similar to Drosophila proteins encoded by hairy and genes in the enhancer of split complex (E-(SPL)-C). Here, we describe the isolation and characterization of Hes6, which encodes a novel WRPW-bHLH protein expressed during neurogenesis in mouse and Xenopus embryos. We show that Hes6 expression follows that of neurogenins but precedes that of the neuronal differentiation genes. We provide several lines of evidence to show that Hes6 expression occurs in developing neurons and is induced by the proneural bHLH proteins but not by the Notch pathway. When ectopically expressed in Xenopus embryos, Hes6 promotes neurogenesis. The properties of Hes6 distinguish it from other members of the WRPW-bHLH family in vertebrates, and suggest that it acts in a positive-feedback loop with the proneural bHLH proteins to promote neuronal differentiation.
The fate of cells in the tailbud of Xenopus laevis
Authors: Davis Robert L. , Kirschner Marc W. 
Published: April 2021

ABSTRACT
The vertebrate tailbud and trunk form very similar tissues. It has been a controversial question for decades whether cell determination in the developing tail proceeds as part of early axial development or whether it proceeds by a different mechanism. To examine this question more closely, we have used photoactivation of fluorescence to mark small neighborhoods of cells in the developing tailbud of Xenopus laevis. We show that, in one region of the tailbud, very small groups of adjacent cells can contribute progeny to the neural tube, notochord and somitic muscle, as well as other identified cell types within a single embryo. Groups averaging three adjacent cells at a later stage can contribute progeny with a similar distribution. Our data suggest that the tailbud contains multipotent cells that make very late germ-layer decisions.
Phosphorylation of Bicoid on MAP-kinase sites: contribution to its interaction with the torso pathway
Authors: Janody Florence , Sturny Rachel , Catala Françoise , Desplan Claude , Dostatni Nathalie 
Published: April 2021

ABSTRACT
The Torso signal transduction pathway exhibits two opposite effects on the activity of the Bicoid (Bcd) morphogen: (i) Bcd function is repressed by Torso (Tor) at the anterior pole of the embryo leading to a retraction of the expression of many Bcd targets from the most anterior region of the embryo, where the Tor tyrosine kinase receptor is activated, and (ii) Bcd function is strengthened by Tor in a broader anterior region, as indicated by a shift of the posterior border of Bcd targets towards the anterior pole in embryos deprived from Tor activity. Anterior repression of Bcd targets was not observed in embryos lacking maternal contribution of D-sor, which acts downstream of Tor and encodes a MAP-kinase kinase. This indicates that the Ras signalling cascade is directly involved in this process, although the known transcriptional effectors of the Tor pathway, tll and hkb, are not (Ronchi, E., Treisman, J., Dostatni, N., Struhl, G. and Desplan, C. (1993) Cell 74, 347-355). Bcd is a good in vitro substrate for phosphorylation by MAP-kinase and phosphorylation of the protein occur in vivo on MAP-kinase sites. In the presence of a Bcd mutant that could no longer be phosphorylated by MAP-kinase, expression of Bcd targets remained repressed by Tor at the pole while strengthening of Bcd activity was reduced. These experiments indicate that phosphorylation of Bcd by MAP-kinase is likely to be required for the Tor pathway to induce its full positive effect on Bcd. This suggests that Tor signalling acts at a distance from the anterior pole by direct modification of the diffusing Bcd morphogen.
Glia dictate pioneer axon trajectories in the Drosophila embryonic CNS
Authors: Hidalgo Alicia , Booth Gwendolen E. 
Published: April 2021

ABSTRACT
Whereas considerable progress has been made in understanding the molecular mechanisms of axon guidance across the midline, it is still unclear how the axonal trajectories of longitudinal pioneer neurons, which never cross the midline, are established. Here we show that longitudinal glia of the embryonic Drosophila CNS direct formation of pioneer axon pathways. By ablation and analysis of glial cells missing mutants, we demonstrate that glia are required for two kinds of processes. Firstly, glia are required for growth cone guidance, although this requirement is not absolute. We show that the route of extending growth cones is rich in neuronal cell bodies and glia, and also in long processes from both these cell types. Interactions between neurons, glia and their long processes orient extending growth cones. Secondly, glia direct the fasciculation and defasciculation of axons, which pattern the pioneer pathways. Together these events are essential for the selective fasciculation of follower axons along the longitudinal pathways.
Positive and negative interactions of GDNF, NTN and ART in developing sensory neuron subpopulations, and their collaboration with neurotrophins
Authors: Baudet Christel , Mikaels Åsa , Westphal Heiner , Johansen Jens , Johansen Teit E. , Ernfors Patrik 
Published: April 2021

ABSTRACT
Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and neublastin/artemin (ART) are distant members of the transforming growth factor β; family, and have been shown to elicit neurotrophic effects upon several classes of peripheral and central neurons. Limited information from in vitro and expression studies has also substantiated a role for GDNF family ligands in mammalian somatosensory neuron development. Here, we show that although dorsal root ganglion (DRG) sensory neurons express GDNF family receptors embryonically, they do not survive in response to their ligands. The regulation of survival emerges postnatally for all GDNF family ligands. GDNF and NTN support distinct subpopulations that can be separated with respect to their expression of GDNF family receptors, whereas ART supports neurons in populations that are also responsive to GDNF or NTN. Sensory neurons that coexpress GDNF family receptors are medium sized, whereas small-caliber nociceptive cells preferentially express a single receptor. In contrast to brain-derived neurotrophic factor (BDNF)-dependent neurons, embryonic nerve growth factor (NGF)-dependent nociceptive neurons switch dependency to GDNF, NTN and ART postnatally. Neurons that survive in the presence of neurotrophin 3 (NT3) or neurotrophin 4 (NT4), including proprioceptive afferents, Merkel end organs and D-hair afferents, are also supported by GDNF family ligands neonatally, although at postnatal stages they lose their dependency on GDNF and NTN. At late postnatal stages, ART prevents survival elicited by GDNF and NTN. These data provide new insights on the roles of GDNF family ligands in sensory neuron development.
Gli2 functions in FGF signaling during antero-posterior patterning
Authors: Brewster R. , Mullor J. L. , Altaba A. Ruiz i 
Published: April 2021

ABSTRACT
Patterning along the anteroposterior (A-P) axis involves the interplay of secreted and transcription factors that specify cell fates in the mesoderm and neuroectoderm. While FGF and homeodomain proteins have been shown to play different roles in posterior specification, the network coordinating their effects remains elusive. Here we have analyzed the function of Gli zinc-finger proteins in mesodermal A-P patterning. We find that Gli2 is sufficient to induce ventroposterior development, functioning in the FGF-brachyury regulatory loop. Gli2 directly induces brachyury, a gene required and sufficient for mesodermal development, and Gli2 is in turn induced by FGF signaling. Moreover, the homeobox gene Xhox3, a critical determinant of posterior development, is also directly regulated by Gli2. Gli3, but not Gli1, has an activity similar to that of Gli2 and is expressed in ventroposterior mesoderm after Gli2. These findings uncover a novel function of Gli proteins, previously only known to mediate hedgehog signals, in the maintenance and patterning of the embryonic mesoderm. More generally, our results suggest a molecular basis for an integration of FGF and hedgehog inputs in Gli-expressing cells that respond to these signals.
Attractive and repulsive interactions between female and male gametophytes in Arabidopsis pollen tube guidance
Authors: Shimizu Kentaro K. , Okada Kiyotaka 
Published: April 2021

ABSTRACT
Sexual reproduction in plants, unlike that of animals, requires the action of multicellular haploid gametophytes. The male gametophyte (pollen tube) is guided to a female gametophyte through diploid sporophytic cells in the pistil. While interactions between the pollen tube and diploid cells have been described, little is known about the intercellular recognition systems between the pollen tube and the female gametophyte. In particular, the mechanisms that enable only one pollen tube to interact with each female gametophyte, thereby preventing polysperm, are not understood. We isolated female gametophyte mutants named magatama (maa) from Arabidopsis thaliana by screening for siliques containing half the normal number of mature seeds. In maa1 and maa3 mutants, in which the development of the female gametophyte was delayed, pollen tube guidance was affected. Pollen tubes were directed to mutant female gametophytes, but they lost their way just before entering the micropyle and elongated in random directions. Moreover, the mutant female gametophytes attracted two pollen tubes at a high frequency. To explain the interaction between gametophytes, we propose a monogamy model in which a female gametophyte emits two attractants and prevents polyspermy. This prevention process by the female gametophyte could increase a plant’s inclusive fitness by facilitating the fertilization of sibling female gametophytes. In addition, repulsion between pollen tubes might help prevent polyspermy. The reproductive isolations observed in interspecific crosses in Brassicaceae are also consistent with the monogamy model.
BMP4 rescues a non-cell-autonomous function ofMsx1in tooth development
Authors: Bei Marianna , Kratochwil Klaus , Maas Richard L. 
Published: April 2021

ABSTRACTThe development of many organs depends on sequential epithelial-mesenchymal interactions, and the developing tooth germ provides a powerful model for elucidating the nature of these inductive tissue interactions. In Msx1-deficient mice, tooth development arrests at the bud stage when Msx1 is required for the expression of Bmp4 and Fgf3 in the dental mesenchyme (Bei, M. and Maas, R. (1998) Development 125, 4325-4333). To define the tissue requirements for Msx1 function, we performed tissue recombinations between wild-type and Msx1 mutant dental epithelium and mesenchyme. We show that through the E14.5 cap stage of tooth development, Msx1 is required in the dental mesenchyme for tooth formation. After the cap stage, however, tooth development becomes Msx1 independent, although our experiments identify a further late function of Msx1 in odontoblast and dental pulp survival. These results suggest that prior to the cap stage, the dental epithelium receives an Msx1-dependent signal from the dental mesenchyme that is necessary for tooth formation.To further test this hypothesis, Msx1 mutant tooth germs were first cultured with either BMP4 or with various FGFs for two days in vitro and then grown under the kidney capsule of syngeneic mice to permit completion of organogenesis and terminal differentiation. Previously, using an in vitro culture system, we showed that BMP4 stimulated the growth of Msx1 mutant dental epithelium (Chen, Y., Bei, M. Woo, I., Satokata, I. and Maas, R. (1996). Development 122, 3035-3044). Using the more powerful kidney capsule grafting procedure, we now show that when added to explanted Msx1-deficient tooth germs prior to grafting, BMP4 rescues Msx1 mutant tooth germs all the way to definitive stages of enamel and dentin formation. Collectively, these results establish a transient functional requirement for Msx1 in the dental mesenchyme that is almost fully supplied by BMP4 alone, and not by FGFs. In addition, they formally prove the postulated downstream relationship of BMP4 with respect to Msx1, establish the non-cell-autonomous nature of Msx1 during odontogenesis, and disclose an additional late survival function for Msx1 in odontoblasts and dental pulp.
Regulation of Drosophila wing vein patterning: net encodes a bHLH protein repressing rhomboid and is repressed by rhomboid-dependent Egfr signalling
Authors: Brentrup Doris , Lerch Hans-Philipp , Jäckle Herbert , Noll Markus 
Published: April 2021

ABSTRACT
The stereotyped pattern of veins in the Drosophila wing is generated in response to local EGF signalling. Mutations in the rhomboid (rho) gene, which encodes a sevenpass membrane protein required to enhance signalling transmitted by the EGF receptor (Egfr), inhibit vein development and disrupt the vein pattern. By contrast, net mutations produce ectopic veins in intervein regions. We have cloned the net gene and show that it encodes a basic HLH protein that probably acts as a transcriptional repressor. net and rho are expressed in mutually exclusive patterns during the development of the wing imaginal disc. Lack of net activity causes rho expression to expand, and vice versa. Furthermore, ectopic expression of net or rho results in their mutual repression and thus suppresses vein formation or generates tube-like wings composed of vein-like tissue. Egfr signalling and net exert mutually antagonising activities during the specification of vein versus intervein fate. While Egfr signalling represses net transcription, net exhibits a two-tiered control by repressing rho transcription and interfering with Egfr signalling downstream of Rho. Our results further suggest that net is required to maintain intervein development by restricting Egfr signalling, which promotes vein development, to the Net-free vein regions of the wing disc.
Evolutionary conservation of redundancy between a diverged pair of forkhead transcription factor homologues
Authors: Molin Laurent , Mounsey Andrew , Aslam Sobia , Bauer Petra , Young Jane , James Martyn , Sharma-Oates Archana , Hope Ian A. 
Published: April 2021

ABSTRACT
The Caenorhabditis elegans gene pes-1 encodes a transcription factor of the forkhead family and is expressed in specific cells of the early embryo. Despite these observations suggesting pes-1 to have an important regulatory role in embryogenesis, inactivation of pes-1 caused no apparent phenotype. This lack of phenotype is a consequence of genetic redundancy. Whereas a weak, transitory effect was observed upon disruption of just T14G12.4 (renamed fkh-2) gene function, simultaneous disruption of the activity of both fkh-2 and pes-1 resulted in a penetrant lethal phenotype. Sequence comparison suggests these two forkhead genes are not closely related and the functional association of fkh-2 and pes-1 was only explored because of the similarity of their expression patterns.
Conservation of the fkh-2/pes-1 genetic redundancy between C. elegans and the related species C. briggsae was demonstrated. Interestingly the redundancy in C. briggsae is not as complete as in C. elegans and this could be explained by alterations of pes-1 specific to the C. briggsae ancestry. With overlapping function retained on an evolutionary time-scale, genetic redundancy may be extensive and expression pattern data could, as here, have a crucial role in characterization of developmental processes.
PIN-FORMED 1 regulates cell fate at the periphery of the shoot apical meristem
Authors: Vernoux Teva , Kronenberger Jocelyne , Grandjean Olivier , Laufs Patrick , Traas Jan 
Published: April 2021

ABSTRACT
The process of organ positioning has been addressed, using the pin-formed 1 (pin1) mutant as a tool. PIN1 is a transmembrane protein involved in auxin transport in Arabidopsis. Loss of function severely affects organ initiation, and pin1 mutants are characterised by an inflorescence meristem that does not initiate any flowers, resulting in the formation of a naked inflorescence stem. This phenotype, combined with the proposed role of PIN1 in hormone transport, makes the mutant an ideal tool to study organ formation and phyllotaxis, and here we present a detailed analysis of the molecular modifications at the shoot apex caused by the mutation. We show that meristem structure and function are not severely affected in the mutant. Major alterations, however, are observed at the periphery of the pin1 meristem, where organ initiation should occur. Although two very early markers of organ initiation, LEAFY and AINTEGUMENTA, are expressed at the periphery of the mutant meristem, the cells are not recruited into distinct primordia. Instead a ring-like domain expressing those primordium specific genes is observed around the meristem. This ring-like domain also expresses a boundary marker, CUP-SHAPED COTYLEDON 2, involved in organ separation, showing that the zone at the meristem periphery has a hybrid identity. This implies that PIN1 is not only involved in organ outgrowth, but that it is also necessary for organ separation and positioning. A model is presented in which PIN1 and the local distribution of auxin control phyllotaxis.
Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1
Authors: Galceran Juan , Miyashita-Lin Emily M. , Devaney Eric , Rubenstein John L. R. , Grosschedl Rudolf 
Published: April 2021

ABSTRACT
Lef1 and other genes of the LEF1/TCF family of transcription factors are nuclear mediators of Wnt signaling. Here we examine the expression pattern and functional importance of Lef1 in the developing forebrain of the mouse. Lef1 is expressed in the developing hippocampus, and LEF1-deficient embryos lack dentate gyrus granule cells but contain glial cells and interneurons in the region of the dentate gyrus. In mouse embryos homozygous for a Lef1-lacZ fusion gene, which encodes a protein that is not only deficient in DNA binding but also interferes with β-catenin-mediated transcriptional activation by other LEF1/TCF proteins, the entire hippocampus including the CA fields is missing. Thus, LEF1 regulates the generation of dentate gyrus granule cells, and together with other LEF1/TCF proteins, the development of the hippocampus.
Formation of corneal endothelium is essential for anterior segment development – a transgenic mouse model of anterior segment dysgenesis
Authors: Reneker Lixing W. , Silversides David W. , Xu Li , Overbeek Paul A. 
Published: April 2021

ABSTRACT
The anterior segment of the vertebrate eye is constructed by proper spatial development of cells derived from the surface ectoderm, which become corneal epithelium and lens, neuroectoderm (posterior iris and ciliary body) and cranial neural crest (corneal stroma, corneal endothelium and anterior iris). Although coordinated interactions between these different cell types are presumed to be essential for proper spatial positioning and differentiation, the requisite intercellular signals remain undefined. We have generated transgenic mice that express either transforming growth factor α (TGFα) or epidermal growth factor (EGF) in the ocular lens using the mouse αA-crystallin promoter. Expression of either growth factor alters the normal developmental fate of the innermost corneal mesenchymal cells so that these cells often fail to differentiate into corneal endothelial cells. Both sets of transgenic mice subsequently manifest multiple anterior segment defects, including attachment of the iris and lens to the cornea, a reduction in the thickness of the corneal epithelium, corneal opacity, and modest disorganization in the corneal stroma. Our data suggest that formation of a corneal endothelium during early ocular morphogenesis is required to prevent attachment of the lens and iris to the corneal stroma, therefore permitting the normal formation of the anterior segment.