bluuebunny/crossref_metadata_2025_split huggingface dataset:
split endsencodes large nuclear proteins that regulate neuronal cell fate and axon extension in theDrosophilaembryo
Authors: Kuang Bing , Wu Sareina C.-Y. , Shin Young-Ah , Luo Liqun , Kolodziej Peter 
Published: April 2021

ABSTRACTsplit ends (spen) encodes nuclear 600 kDa proteins that contain RNA recognition motifs and a conserved C-terminal sequence. These features define a new protein family, Spen, which includes the vertebrate MINT transcriptional regulator. Zygotic spen mutants affect the growth and guidance of a subset of axons in the Drosophila embryo. Removing maternal and zygotic protein elicits cell-fate and more general axon-guidance defects that are not seen in zygotic mutants. The wrong number of chordotonal neurons and midline cells are generated, and we identify defects in precursor formation and EGF receptor-dependent inductive processes required for cell-fate specification. The number of neuronal precursors is variable in embryos that lack Spen. The levels of Suppressor of Hairless, a key transcriptional effector of Notch required for precursor formation, are reduced, as are the nuclear levels of Yan, a transcriptional repressor that regulates cell fate and proliferation downstream of the EGF receptor. We propose that Spen proteins regulate the expression of key effectors of signaling pathways required to specify neuronal cell fate and morphology.
Drosophila Atonal controls photoreceptor R8-specific properties and modulates both Receptor Tyrosine Kinase and Hedgehog signalling
Authors: White Neil M. , Jarman Andrew P. 
Published: April 2021

Abstract
During Drosophila eye development, the proneural gene atonal specifies founding R8 photoreceptors of individual ommatidia, evenly spaced relative to one another in a pattern that prefigures ommatidial organisation in the mature compound eye. Beyond providing neural competence, however, it has remained unclear to what extent atonal controls specific R8 properties. We show here that reduced Atonal function gives rise to R8 photoreceptors that are functionally compromised: both recruitment and axon pathfinding defects are evident. Conversely, prolonged Atonal expression in R8 photoreceptors induces defects in inductive recruitment as a consequence of hyperactive EGFR signalling. Surprisingly, such prolonged expression also results in R8 pattern formation defects in a process associated with both Hedgehog and Receptor Tyrosine Kinase signalling. Our results strongly suggest that Atonal regulates signalling and other properties of R8 precursors.
The essential Mcm7 protein PROLIFERA is localized to the nucleus of dividing cells during the G1 phase and is required maternally for early Arabidopsis development
Authors: Springer Patricia S. , Holding avid R. , Groover Andrew , Yordan Cristina , Martienssen Robert A. 
Published: April 2021

ABSTRACT
PROLIFERA (PRL) encodes a homologue of the DNA replication licensing factor Mcm7, a highly conserved protein found in all eukaryotes. Insertions in the PROLIFERA gene are lethal, resulting in decreased transmission through the female gametophyte, and homozygous embryonic lethality. We show here that PROLIFERA is specifically expressed in populations of dividing cells in sporophytic tissues of the plant body, such as the palisade layer of the leaf and founder cells of initiating flower primordia. Gene fusions with the green fluorescent protein (GFP) reveal that the PROLIFERA protein accumulates during the G1 phase of the cell cycle, and is transiently localized to the nucleus. During mitosis, the fusion protein rapidly disappears, returning to daughter nuclei during G1. PROLIFERA∷GUS fusions are strongly expressed in the central cell nucleus of mature megagametophytes, which have a variety of arrest points reflecting a leaky lethality. Expression is also observed in the endosperm of mutant prl embryo sacs that arrest following fertilization. Crosses with wild-type pollen result in occasional embryonic lethals that also stain for GUS activity. In contrast, embryos resulting from crosses of wild-type carpels with PRL∷GUS pollen do not stain and are phenotypically normal. In situ hybridization of GUS fusion RNA indicates transcription is equivalent from maternally and paternally derived alleles, so that accumulation of maternally derived gametophytic protein is likely to be responsible for the ‘maternal’ effect.
Movie available on-line: http://www.biologists.com/Development/movies/dev0284.html
Chip is an essential cofactor for Apterous in the regulation of axon guidance in Drosophila
Authors: Meyel Donald J. van , O’Keefe David D. , Thor Stefan , Jurata Linda W. , Gill Gordon N. , Thomas John B. 
Published: April 2021

ABSTRACT
LIM-homeodomain transcription factors are expressed in subsets of neurons and are required for correct axon guidance and neurotransmitter identity. The LIM-homeodomain family member Apterous requires the LIM-binding protein Chip to execute patterned outgrowth of the Drosophila wing. To determine whether Chip is a general cofactor for diverse LIM-homeodomain functions in vivo, we studied its role in the embryonic nervous system. Loss-of-function Chip mutations cause defects in neurotransmitter production that mimic apterous and islet mutants. Chip is also required cell-autonomously by Apterous-expressing neurons for proper axon guidance, and requires both a homodimerization domain and a LIM interaction domain to function appropriately. Using a Chip/Apterous chimeric molecule lacking domains normally required for their interaction, we reconstituted the complex and rescued the axon guidance defects of apterous mutants, of Chip mutants and of embryos doubly mutant for both apterous and Chip. Our results indicate that Chip participates in a range of developmental programs controlled by LIM-homeodomain proteins and that a tetrameric complex comprising two Apterous molecules bridged by a Chip homodimer is the functional unit through which Apterous acts during neuronal differentiation.
The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium
Authors: Sukegawa Akiko , Narita Tomohiro , Kameda Takashi , Saitoh Kanako , Nohno Tsutomu , Iba Hideo , Yasugi Sadao , Fukuda Kimiko 
Published: April 2021

ABSTRACT
The embryonic gut of vertebrates consists of endodermal epithelium, surrounding mesenchyme derived from splanchnic mesoderm and enteric neuronal components derived from neural crest cells. During gut organogenesis, the mesenchyme differentiates into distinct concentric layers around the endodermal epithelium forming the lamina propria, muscularis mucosae, submucosa and lamina muscularis (the smooth muscle layer). The smooth muscle layer and enteric plexus are formed at the outermost part of the gut, always some distance away from the epithelium. How this topographical organization of gut mesenchyme is established is largely unknown. Here we show the following: (1) Endodermal epithelium inhibits differentiation of smooth muscle and enteric neurons in adjacent mesenchyme. (2) Endodermal epithelium activates expression of patched and BMP4 in adjacent non-smooth muscle mesenchyme, which later differentiates into the lamina propria and submucosa. (3) Sonic hedgehog (Shh) is expressed in endodermal epithelium and disruption of Shh-signaling by cyclopamine induces differentiation of smooth muscle and a large number of neurons even in the area adjacent to epithelium. (4) Shh can mimic the effect of endodermal epithelium on the concentric stratification of the gut. Taken together, these data suggest that endoderm-derived Shh is responsible for the patterning across the radial axis of the gut through induction of inner components and inhibition of outer components, such as smooth muscle and enteric neurons.
Multiple roles for Gata5 in zebrafish endoderm formation
Authors: Reiter Jeremy F. , Kikuchi Yutaka , Stainier Didier Y. R. 
Published: April 2021

ABSTRACT
Previous studies have indicated that gata5, a zinc-finger transcription factor gene, is required for the development of the zebrafish gut tube. Here, we show that gata5 mutants also display defects in the development of other endodermal organs such as the liver, pancreas, thyroid and thymus. gata5 is expressed in the endodermal progenitors from late blastula stages, suggesting that it functions early during endoderm development. We indeed find that during gastrulation stages, gata5 mutants form fewer endodermal cells than their wild-type siblings. In addition, the endodermal cells that form in gata5 mutants appear to express lower than wild-type levels of endodermal genes such as sox17 and axial/foxA2. Conversely, overexpression of gata5 leads to expanded endodermal gene expression. These data indicate that Gata5 is involved both in the generation of endodermal cells at late blastula stages and in the maintenance of endodermal sox17 expression during gastrulation.
We have also analyzed the relationship of Gata5 to other factors involved in endoderm formation. Using complementary mutant and overexpression analyses, we show that Gata5 regulates endoderm formation in cooperation with the Mix-type transcription factor Bon, that Gata5 and Bon function downstream of Nodal signaling, and that cas function is usually required for the activity of Gata5 in endoderm formation. Finally, we show that fau/gata5, bon and cas exhibit dominant genetic interactions providing additional support that they function in the same pathway. Together, these data demonstrate that Gata5 plays multiple roles in endoderm development in zebrafish, and position Gata5 relative to other regulators of endoderm formation.
Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis
Authors: Ishikawa Tomo-o , Tamai Yoshitaka , Zorn Aaron M. , Yoshida Hisahiro , Seldin Michael F. , Nishikawa Shin-ichi , Taketo Makoto M. 
Published: April 2021

ABSTRACT
Wnts are secreted signaling molecules implicated in various developmental processes and frizzled proteins are the receptors for these Wnt ligands. To investigate the physiological roles of frizzled proteins, we isolated and characterized a novel mouse frizzled gene Fzd5. Fzd5 mRNA was expressed in the yolk sac, eye and lung bud at 9.5 days post coitum. Fzd5 specifically synergized with Wnt2, Wnt5a and Wnt10b in ectopic axis induction assays in Xenopus embryos. Using homologous recombination in embryonic stem cells, we have generated Fzd5 knockout mice. While the heterozygotes were viable, fertile and appeared normal, the homozygous embryos died in utero around 10.75 days post coitum, owing to defects in yolk sac angiogenesis. At 10.25 days post coitum, prior to any morphological changes, endothelial cell proliferation was markedly reduced in homozygous mutant yolk sacs, as measured by BrdU labeling. By 10.75 days post coitum, large vitelline vessels were poorly developed, and the capillary plexus was disorganized. At this stage, vasculogenesis in the placenta was also defective, although that in the embryo proper was normal. Because Wnt5a and Wnt10b co-localized with Fzd5 in the developing yolk sac, these two Wnts are likely physiological ligands for the Fzd5-dependent signaling for endothelial growth in the yolk sac.
Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo
Authors: Dyer Michael A. , Farrington Sarah M. , Mohn Deanna , Munday James R. , Baron Margaret H. 
Published: April 2021

ABSTRACT
During gastrulation in the mouse, mesoderm is induced and patterned by secreted signaling molecules, giving rise first to primitive erythroblasts and vascular endothelial cells. We have demonstrated previously that development of these lineages requires a signal(s) secreted from the adjacent primitive endoderm. We now show that Indian hedgehog (Ihh) is a primitive endoderm-secreted signal that alone is sufficient to induce formation of hematopoietic and endothelial cells. Strikingly, as seen with primitive endoderm, Ihh can respecify prospective neural ectoderm (anterior epiblast) along hematopoietic and endothelial (posterior) lineages. Downstream targets of the hedgehog signaling pathway (the genes encoding patched, smoothened and Gli1) are upregulated in anterior epiblasts cultured in the presence of Ihh protein, as is Bmp4, which may mediate the effects of Ihh. Blocking Ihh function in primitive endoderm inhibits activation of hematopoiesis and vasculogenesis in the adjacent epiblast, suggesting that Ihh is an endogenous signal that plays a key role in the development of the earliest hemato-vascular system. To our knowledge, these are the earliest functions for a hedgehog protein in post-implantation development in the mouse embryo.
Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis
Authors: Kalev-Zylinska Maggie L. , Horsfield Julia A. , Flores Maria Vega C. , Postlethwait John H. , Vitas Maria R. , Baas Andrea M. , Crosier Philip S. , Crosier Kathryn E. 
Published: April 2021

RUNX1/AML1/CBFA2 is essential for definitive hematopoiesis, and chromosomal translocations affecting RUNX1 are frequently involved in human leukemias. Consequently, the normal function of RUNX1 and its involvement in leukemogenesis remain subject to intensive research. To further elucidate the role of RUNX1 in hematopoiesis, we cloned the zebrafish ortholog (runx1) and analyzed its function using this model system. Zebrafish runx1 is expressed in hematopoietic and neuronal cells during early embryogenesis. runx1 expression in the lateral plate mesoderm co-localizes with the hematopoietic transcription factor scl, and expression of runx1 is markedly reduced in the zebrafish mutants spadetail and cloche. Transient expression of runx1 in cloche embryos resulted in partial rescue of the hematopoietic defect. Depletion of Runx1 with antisense morpholino oligonucleotides abrogated the development of both blood and vessels, as demonstrated by loss of circulation, incomplete development of vasculature and the accumulation of immature hematopoietic precursors. The block in definitive hematopoiesis is similar to that observed in Runx1 knockout mice, implying that zebrafish Runx1 has a function equivalent to that in mammals. Our data suggest that zebrafish Runx1 functions in both blood and vessel development at the hemangioblast level, and contributes to both primitive and definitive hematopoiesis. Depletion of Runx1 also caused aberrant axonogenesis and abnormal distribution of Rohon-Beard cells, providing the first functional evidence of a role for vertebrate Runx1 in neuropoiesis.To provide a base for examining the role of Runx1 in leukemogenesis, we investigated the effects of transient expression of a human RUNX1-CBF2T1 transgene [product of the t(8;21) translocation in acute myeloid leukemia] in zebrafish embryos. Expression of RUNX1-CBF2T1 caused disruption of normal hematopoiesis, aberrant circulation, internal hemorrhages and cellular dysplasia. These defects reproduce those observed in Runx1-depleted zebrafish embryos and RUNX1-CBF2T1 knock-in mice. The phenotype obtained with transient expression of RUNX1-CBF2T1 validates the zebrafish as a model system to study t(8;21)-mediated leukemogenesis.
A study of the influence of isolated calf spleen RNA on amphibian histogenesis
Authors: Finnegan Cyril V. , Biggin William P. 
Published: April 2021

ABSTRACTRibonucleic acid (RNA) was isolated from calf spleen tissue by the new Kirby procedure followed by three phenol washings to reduce the peptide-protein contamination. Ultraviolet absorption spectra and colorimetric analyses indicated the reduction or absence of protein, peptide, DNA and, after methoxyethanol purification, polysaccharide from the isolated RNA. Ultracentrifuge sedimentation analysis showed three components in the undegraded RNA isolate: a 27S fraction, an 18S fraction and a 7-8S fraction. This ribosomal-messenger RNA was added to non-nutrient medium for induction testing. Neither embryos nor competent gastrula ectoderm of Xenopus laevis demonstrated, in a limited series, any tissue-specific inductive response, but both experimental systems in the RNA-conditioned medium did demonstrate enhanced epithelial development as compared with the control systems. Postgastrula stages of Taricha torosa and Ambystoma gracile exposed during development to reagent-grade beef liver s-RNA demonstrated hyperplasia in the dorsal mesencephalon-rhombencephalon and the anterior neural crest mesenchyme population along with an enhancement of auditory and posterior entodermal epithelial development.
The molars of the tabby mouse, and a test of the ‘single-active X-chromosome’ hypothesis
Authors: Grüneberg Hans 
Published: April 2021

ABSTRACT
The sex-linked gene for tabby (Ta) in the mouse, in addition to its effects on fur and skin, has a characteristic dental syndrome (Griineberg, 1965). Some tabby heterozygotes have a spectacular mixture of molar teeth, some of which are normal, others which are tabby, and some which combine features of both. This prima facie evidence in favour of the single-active X-chromosome hypothesis of Lyon (1961) can be turned into a more exacting quantitative test of that concept. An autosomal mimic of tabby, called crinkled (cr; linkage group 14), with the same dental syndrome, offers opportunities for further tests of the hypothesis. It will be seen that, contrary to first impressions, the quantitative study reveals a situation which is not in agreement with the Lyon hypothesis.
The developmental endocrinology of the spleen in chicken embryos: II. The pars distalis and splenomegaly
Authors: Goldberg R. B. , Betz T. W. 
Published: April 2021

ABSTRACTPars distalis-extract treatment of intact or ‘hypophysectomized’ chicken embryos resulted in a splenomegaly, perhaps of a host-versus-graft nature, by 17 and 17·5 days of incubation. Pars distalis grafts in intact embryos reduced spleen size, encouraged white-pulp follicle formation, but ‘suppressed’ red-pulp development. Adult spleen extract and bovine serum albumin did not change spleen sizes or histology appreciably in intact embryos.Perhaps pars distalis hormones inhibit red-pulp development or stimulate white-pulp follicles which may compete with red-pulp proliferation but encourage splenic vasculogenesis alone or by stimulating adrenocorticoid, thyroid, and other hormone levels while other extract factors cause splenomegaly.
Oogenesis in Tenebrio molitor: Histological and autoradiographical observations on pupal and adult ovaries
Authors: Ullmann Suzanne L. 
Published: April 2021

ABSTRACT
Nurse cells and oocytes in the telotiophic ovary of Tenebrio molitor L. (Insecta, Coleoptera-Polyphaga) are differentiated in the larval stadium. During pupation DNA synthesis occurs in the nurse cells and is probably associated with polyploidy; some of them become multinucleate. The functional significance of these events is interpreted as preparation for subsequent massive RNA synthesis. The oviducts incorporate [3H]thymidine and undergo elongation due to mitoses. This ceases at eclosion. RNA synthesis in the pupal ovary is low, but increases in the nurse cells and follicle cells just prior to eclosion. In the adult ovary, once the growth phase has been initiated, a primary oocyte takes about six days to reach maturity. The nurse cells, though apparently lacking nucleoli, synthesize much stable RNA which reaches each oocyte via a trophic cord. The follicle cells undergo continuous DNA synthesis: some nuclei contain over 64 times the haploid amount of DNA. Replication is probably asynchronous within a nucleus: this may account for the phenomenon of simultaneous DNA and RNA synthesis in the follicle cells, which also lack nucleoli. Oogenesis has been divided into nine developmental stages, three of which are vitellogenic. The oocyte chromosomes are capable of RNA synthesis both when despiralized during early previtellogenesis and after karyosome formation, which occurs at stage 6. The protein content of the oocyte appears to have a dual origin: at least part of the ooplasmic proteins form in situ; while yolk proteins are derived from the haemolymph. The extra-ovarian protein reaches the oocyte via spaces which develop between the follicle cells. The nucleoplasm becomes more heavily labelled with proteins than the ooplasm. With [3H]leucine, methionine and phenylalanine but not with tryptophane or arginine, there is an increased incorporation into the karyosome. It is suggested that this karyosomeassociated protein may function in gene masking. The significance of these findings is discussed with reference to the literature.
The development of dorsal root ganglia and ventral horns in the opossum. A quantitative study
Authors: Hughes Arthur 
Published: April 2021

ABSTRACTNumbers of cells, of mitotic figures, and of degeneration sites have been counted in dorsal root ganglia and ventral horns during the development of the opossum, from embryonic to pouch-young stages.Tn the embryo, from forelimb bud stages onwards, the cervico-brachial ganglia growrapidly, at first with very high mitotic rates (about 5 %) and little cell degeneration. One day before birth, cell death is widespread through the whole series though cell numbers at all levels continue to increase. In the new-born, the growth of brachial ganglia is checked by very high local rates of cell death.In the cord, cells of the lateral motor columns, or ventral horns arise by outward migration of cells from the basal half of the mantle layer. In the later embryo, these cells are recognizable at cervico-brachial levels during their migration, and are then accompanied by de-generating cells, the axial distribution of which foreshadows that of the lateral column of the new-born.In the pouch-young, there is a slow loss of neurons from dorsal root ganglia and from ventral horns. This begins later at lumbo-sacral than at cervico-brachial levels.Comparison of these results with data from other species emphasizes the variety of patterns in neural development among tetrapods.
Effects of insulin insufficiency on forelimb and tail regeneration in adultDiemictylus viridescens
Authors: Vethamany-Globus Swani , Liversage Richard A. 
Published: April 2021

ABSTRACTExperimental diabetes caused by pancreatectomy resulted in a marked interference in limb and tail regeneration in adult newts. Under pancreatic insufficiency, throughout the entire period of regeneration, limb and tail regenerates (26 days old) consistently showed sparse population of blastema cells, while older regenerates (58–79 days) exhibited severe abnormalities. Newts with these abnormal regenerates always had an atrophied pancreas. In the event that the cauterized pancreas regenerated, there was a subsequent recuperation in the regeneration processes of the appendages. Our data strongly indicates that a correlation exists between the normal (intact) pancreas and regeneration of the limb and tail in the adult newt.In addition, alloxanization inhibited normal limb and tail regeneration. Again, recuperation of the pancreas from the effects of alloxan was followed by restoration of limb and tail regeneration. These results suggest an insulin role in the hormone control of regeneration. The possible actions of insulin are discussed.