pinecone/core-2020-05-10-deduplication huggingface dataset:
biparous:A Novel bHLH Gene Expressed in Neuronal and Glial Precursors inDrosophila

AbstractGenetic studies have uncovered many genes that are involved in the first steps of neuronal development inDrosophila.Less is known about the intermediate steps during which individual precursor cells follow either the neuronal pathway or the glial pathway. We report the identification of a novel bHLH gene,biparous,expressed in neuronal and glial precursors inDrosophila.Unlike most bHLH genes,biparousexpression continues to the final stages of neurogenesis in the embryo. Expression ofbiparousis not observed in end stage postmitotic neurons and precedes the expression ofrepo,a gene activated in later stages of glial differentiation. The bHLH domain is sufficiently different from previously described bHLH domains to imply a novel function
Embryonic Heart and Skin Defects in Mice Lacking Plakoglobin

AbstractPlakoglobin is the only component common to both the desmosomal plaque and the cadherin–catenin cell adhesion complex in the adherens junction. It is highly homologous to vertebrate β-catenin and toDrosophilaarmadillo protein and may—like these proteins—be also involved in signaling pathways. To analyze the role of plakoglobin during mouse development we inactivated theplakoglobingene by homologous recombination in embryonic stem cells and generated transgenic mice.Plakoglobinnull-mutant embryos died from Embryonic Day 10.5 onward, due to severe heart defects. Some mutant embryos developed further, especially on a C57BL/6 genetic background, and died around birth, presumably due to cardiac dysfunction, and with skin blistering and subcorneal acantholysis. Ultrastructural analysis revealed that here desmosomes were greatly reduced in number and structurally altered. Thus, using reversed genetics we demonstrate that plakoglobin is an essential structural component for desmosome function. The skin phenotype in plakoglobin-deficient mice is reminiscent of the human blistering disease, epidermolytic hyperkeratosis
Genes Required for GLP-1 Asymmetry in the EarlyCaenorhabditis elegansEmbryo

AbstractThe translation of maternalglp-1mRNA is regulated both temporally and spatially in the earlyCaenorhabditis elegansembryo (T. C. Evans, S.L. Crittenden, V. Kodoyianni, and J. Kimble,Cell77, 183–194, 1994). To investigate the control of embryonicglp-1expression, we have examined the distribution of GLP-1 protein in selected maternal effect mutants that affect pattern or fate in the early embryo. We find that mutants that disrupt anterior–posterior asymmetry in the early embryo (par-1–par-6, emb-8,Par(q537)) disrupt the spatial but not temporal control of GLP-1 expression: GLP-1 is observed at the normal stage of embryogenesis inpar-like mutants; however, it is uniformly distributed. In contrast, mutants that alter blastomere identity (skn-1, pie-1, mex-1, apx-1) do not affect the normal GLP-1 pattern. We conclude that genes controlling the asymmetry of cellular components, including P granules, also control GLP-1 asymmetry in the early embryo. The finding that mutants that disrupt anterior–posterior asymmetry translate GLP-1 in all blastomeres suggests that loss of embryonic asymmetry causes translational activation of GLP-1 in the posterior
Xbap,a Vertebrate Gene Related tobagpipe, Is Expressed in Developing Craniofacial Structures and in Anterior Gut Muscle

AbstractTheDrosophila bagpipe (bap)gene is involved in the specification of the musculature of the embryonic midgut. We report the isolation and characterization of aXenopussequence,Xbap,which is closely related tobap. Xbapis also expressed in the developing musculature of the midgut, suggesting that this developmental role ofbagpipeis evolutionarily conserved. However, a second, novel role in development is suggested by the observation thatXbapis also expressed in a region of the developing facial cartilage. Using a combination of cartilage staining and comparison to thegoosecoidhead expression pattern, we show thatXbapexpression marks the precursors to the basihyobranchial, palatoquadrate, and possibly Meckel's cartilages. This vertebratebagpipesequence therefore is expressed in both mesodermally and neural crest-derived tissues
Soma–Germ Cell Interactions inCaenorhabditis elegans:Multiple Events of Hermaphrodite Germline Development Require the Somatic Sheath and Spermathecal Lineages

AbstractGerm cells complete multiple events to form functional oocytes and sperm. In theCaenorhabditis eleganshermaphrodite, germ cells develop in proximity to the somatic gonad sheath and spermathecal cells. We present evidence from cellular laser ablation studies indicating that cells of the somatic sheath and spermathecal lineages play critical roles in four events of hermaphrodite germline development. (1) Cells of the sheath and spermathecal lineage support germline proliferation; ablation of sheath/spermathecal precursor cells reduces mitotic proliferation. (2) These cells also play a role in the exit of germ cells from the pachytene stage of meiotic prophase and/or gamete differentiation; ablation can result in undifferentiated germ cells arrested in pachytene. (3) Proximal sheath and distal spermatheca cells are required for ovulation of the oocyte. During wild-type ovulation, the mature oocyte is expelled from the gonad arm by contraction of the proximal myoepithelial sheath and dilation of the distal spermatheca. Ablation of these cells traps mature oocytes in the gonad arm where they endomitotically replicate their DNA (the Emo phenotype). (4) Cells of the sheath and spermathecal lineage also appear to promote the male germ cell fate since ablation of one sheath/spermathecal precursor cell can feminize the hermaphrodite germ line. These somatic ablation-induced germline phenotypes demonstrate that the somatic gonad is required for multiple events inC. elegansgermline development. Further, these results suggest that soma to germline cell–cell interactions inC. elegansare physiological in character (i.e., contraction during ovulation) as well as regulatory
Mechanisms of Evolutionary Changes in Timing, Spatial Expression, and mRNA Processing in themsp130Gene in a Direct-Developing Sea Urchin,Heliocidaris erythrogramma

AbstractDevelopmental processes associated with skeletogenesis differ in the direct-developing sea urchinHeliocidaris erythrogrammafrom that inHeliocidaris tuberculataand other indirect-developing species. InH. erythrogramma,the differences include ingression of a much higher number of mesenchyme cells, failure of the cells to form the typical ring pattern of cells prior to the onset of skeletogenesis, a significantly reduced larval skeleton, and a delay in timing of expression of the skeletogenic cell-restricted genemsp130.We report that the heterochronic change inmsp130expression is regulated at the level of transcription. By transient expression of reporter constructs containingmsp130promoter regions from direct- and indirect-developing species, we found that this evolutionary change in regulation is consistent with changes in the timing of action oftrans-acting factors in skeletogenic mesenchyme cells. We further used these experiments to show that theH. erythrogrammapromoter contains elements required for correct spatial expression in the primary mesenchyme cells of an indirect-developing host. We finally show that alternate processing ofH. erythrogramma msp130is thus far specific to this species and not an aspect of adult skeletogenesis
GATA-2 Is a Maternal Transcription Factor Present inXenopusOocytes as a Nuclear Complex Which Is Maintained throughout Early Development

AbstractWe show thatXenopusoocytes and embryos contain GATA-2, stored in nuclei as a non-chromatin-bound complex. Its binding site specificity is different from that of GATA-1, having a much higher affinity for the motif with a core GATC sequence. This binding site preference was markedly reduced by either release of the factor with deoxycholate or purification on a DNA affinity column, suggesting a role for a cofactor(s). The identity of the maternal GATA factor was established as GATA-2 in two ways: (1) binding to an oligonucleotide probe was abolished by inclusion of either of two GATA-2 monoclonal antibodies, and (2) a protein of correct molecular weight for GATA-2 was detected by immunoblotting with a polyclonal antibody raised against aXenopusGATA-2-specific peptide. Although predominantly complexed, some of the oocyte GATA-2 is functional as a transcription factor because the transcriptional activity of the chicken βH-globin promoter injected into oocytes was reduced by mutation of either of two GATA binding sites. This effect was more pronounced when the stronger of the two sites was mutated. Butyrate treatment of oocytes stimulated cap-site initiation by up to 17-fold with both normal promoter and GATA site mutant constructs, showing that the mechanism of butyrate stimulation is not via GATA-2. The possible significance of regulating the availability of maternal GATA-2 during early development is discussed
Misexpression ofnautilusInduces Myogenesis in Cardioblasts and Alters the Pattern of Somatic Muscle Fibers

Abstractnautilus(nau), one member of the myogenic regulatory family of bHLH-encoding genes, is expressed in a subset of muscle precursors and differentiated fibers in theDrosophilaembryo. To elucidate the role ofnautilusin myogenesis, we have misexpressed it using the GAL4-targeted system. We find that ectopic expression results in lethality throughoutDrosophiladevelopment. We analyzed the effects of embryonic expression in mesodermal tissues that include the cardioblasts of the dorsal vessel as well most, if not all, of the presumptive somatic muscle precursors. Immunohistochemical staining for muscle MHC revealed abnormalities that include an absence of cardial cells, coincident with the appearance of novel muscle fibers adjacent to the dorsal vessel. Moreover, many cardioblasts express increased levels of muscle-specific genes such as myosin, actin 57B, and Mlp60A, a protein that is restricted to the somatic, visceral, and pharyngeal muscles. These data suggest that the missing cardial cells have been transformed into cells with properties similar to those of the somatic muscles. In addition, ubiquitous expression ofnautilusin somatic muscle cells of these embryos resulted in muscle pattern defects. Specifically, muscles that do not normally expressnautiluswere frequently absent, and novel fibers were observed in positions reminiscent ofnau-expressing muscles. These data imply thatnautiluscan alter the developmental program of muscle precursors. In summary, we suggest thatnautilusinduces myogenic differentiationin vivowhen ectopically expressed in developing cardioblasts and may affect the myogenic differentiation program of specific muscle fibers
Agrin Inhibits Neurite Outgrowth but Promotes Attachment of Embryonic Motor and Sensory Neurons

AbstractAgrin is a secreted glycoprotein with the ability to cluster cell surface molecules, including the nicotinic acetylcholine receptor (AchR) on muscle cells. Alternate splicing of agrin mRNA results in a family of agrin proteins which differ in their clustering potency. Neuronal-specific isoforms with the highest clustering activity play a role in clustering postsynaptic proteins at the neuromuscular junction. However, the function of agrin isoforms expressed in many nonneuronal tissues, and only weakly active in clustering assays, remains obscure. Monolayer cultures of Chinese hamster ovary (CHO) cells expressing a neuronal (agrin-19) or a nonneuronal (agrin-0) form of agrin were used to assay the effect of agrin on neurite outgrowth and cell attachment. These results were compared to outgrowth on control CHO cells expressing only drug resistance and on regions of CHO–agrin monolayers not expressing detectable levels of agrin. Neurite extension on confluent monolayers of agrin-0- or -19-expressing CHO cells was reduced substantially below that of controls. In one experiment neurite lengths were compared at 2 and 3 days after plating and suggested that neurite outgrowth may be stopped and not simply retarded. Attachment of sensory or motoneurons was nearly twofold higher to agrin monolayers than to control cells, showing that the inhibition is not a result of a nonpermissive environment. An agrin construct missing the C-terminal half, removing the major site of variability and clustering activity, was also tested. This construct did not reduce outgrowth, suggesting that the C-terminal half of the protein may be important in stopping growth as well as inducing clustering. These results expand the role of agrin in synaptogenesis as it may provide a stop signal at the myofiber surface and may anchor the presynaptic fibers to the eventual motor endplate
Short-Range Cell–Cell Signals Control Ectodermal Patterning in the Oral Region of the Sea Urchin Embryo

AbstractThe ectoderm of the sea urchin embryo has been a useful system for understanding how regions of a simple epithelium are specified during early development, as well as how pattern formation leads to the correct localization of mesenchyme cells during morphogenesis. This study examines cell–cell signals that regulate precise patterning of ectoderm within the oral region of embryos of the sea urchin,Lytechinus variegatus.The oral ectoderm contains at least two types of patterned tissues: (1) the ectoderm that forms the stomodeum and (2) ectoderm expressing pattern information required for formation of parallel oral skeletal rods by primary mesenchyme cells (PMCs). Using microsurgical isolations and cell transplantation, we show (1) that cell–cell signaling is capable of producing new oral ectodermal structures until immediately prior to the gastrula stage, (2) that the presumptive oral ectoderm is not committed to produce oral structures until the early gastrula stage, (3) that oral ectodermal patterning cues for PMCs are highly local in character, and (4) that interactions between the tip of the archenteron and the presumptive oral ectoderm are not required for the differentiation of cells within either tissue. These studies suggest that short-range cell–cell signals within the ectoderm are involved in specifying regionalized oral ectodermal tissues immediately prior to gastrulation, and that this patterned ectoderm then influences the localization of skeletogenic mesenchyme cells in the oral region
The Neurite-Promoting Effect of Laminin Is Mediated by Different Mechanisms in Embryonic and Adult Regenerating Mouse Optic Axonsin Vitro

AbstractRetinal explants from embryonic or adult mice were placed on laminin or merosin substrates and the outgrowth of optic fibers was assayed under serum-free conditions. Both substrates strongly promoted outgrowth. A blocking antibody to the β1/β3 integrin subunits completely blocked laminin-dependent growth of embryonic optic fibers but had no detectable effect on adult fibers. Similarly, a blocking antibody against the main neurite-promoting region within the globular domain of the E8 fragment of laminin inhibited growth of embryonic fibers but had no effect on adult optic fibers. The β1 integrin subunit was identified immunohistochemically on both embryonic and adult fibers. These findings indicate that adult fibers have lost the β1 function which dominates laminin-dependent growth in embryonic fibers but express a receptor for laminin-dependent growth that is not detectable in embryonic fibers. These findings suggest that there are intrinsic differences between embryonic and adult optic fibers that may have implications for regenerative failure in the central nervous system of adult mammals
State of Commitment of Prospective Neural Plate and Prospective Mesoderm in Late Gastrula/Early Neurula Stages of Avian Embryos

AbstractWe examined the ability of epiblast regions of known prospective fate from the late gastrula/early neurula stage of avian embryos to self-differentiate when placed heterotopically, testing their state of commitment. Three sites were examined: paranodal prospective neural plate ectoderm, containing cells fated to form a portion of the lateral wall of the neural tube at essentially all rostrocaudal levels of the neuraxis; prospective mesoderm from the caudolateral epiblast, containing cells fated to ingress through the primitive streak and to form lateral plate mesoderm; and prospective mesoderm from one level of the primitive streak, containing cells fated to continue ingressing and form paraxial mesoderm. Grafts from all sites exhibited plasticity. Grafts from the prospective neural plate ectoderm could readily substitute for regions of prospective mesoderm, when transplanted to either the epiblast or primitive streak, undergoing an epithelial–mesenchymal transition and, where appropriate, expressingparaxis,a gene expressed in paraxial mesoderm. Similarly, grafts containing prospective mesoderm from the epiblast could readily substitute for regions of the prospective neural plate ectoderm, undergoing convergent-extension movements characteristic of neuroectodermal cells and expressing appropriate genes such asEngrailed-2andHoxb-1.Grafts containing prospective mesoderm from the primitive streak could also incorporate into the neural plate and undergo convergence-extension movements of neurulation, although their principal contribution was to mesodermal and endodermal structures. Collectively, our results demonstrate that at the late gastrula/early neurula stage, germ layer-specific properties are not irrevocably fixed for prospective ectodermal and mesodermal regions of the blastoderm. Moreover, the signals responsible for the induction of these two tissue types must still be present and available at these late stages
Targeted Mutations inHoxa-9andHoxb-9Reveal Synergistic Interactions

AbstractMice were generated with a targeted disruption of the homeobox-containing genehoxb-9.Mice homozygous for this mutation show defects in the development of the first and second ribs. In most cases the first and second ribs are fused near the point at which the first and second pairs of ribs normally attach to the sternum. Abnormalities of the sternum accompany the rib fusions. These include abnormal attachment of the ribs to the sternum, a reduction in the number of intercostal segments of the sternum, and abnormal growth of the intercostal segments. Over half of the homozygous mutants, as well as some heterozygotes, also have an eighth rib attached to the sternum. These results show thathoxb-9plays a significant role in the specification of thoracic skeletal elements. To reveal potential interactions between the paralogousHoxgeneshoxa-9andhoxb-9,mice heterozygous for both mutations were intercrossed. Mice homozygous for both mutations show more severe phenotypes than predicted by the addition of the individual mutant phenotypes. Both the penetrance and the expressivity of the rib and sternal defects are increased, suggesting synergistic interactions between these genes. In particular, the sternum defects are greatly exacerbated. Interestingly, the defects inhoxb-9andhoxa-9/hoxb-9mutant mice are concentrated along the axial column at points of transition between vertebral types
Distinct Stress-Inducible and Developmentally Regulated Heat Shock Transcription Factors inXenopusOocytes

AbstractThe presence of a maternal pool of heat shock factor (HSF) inXenopusoocytes has been suggested by two lines of evidence from previous studies. First, heat shock response element (HSE)-binding activity is induced in heat-shocked eggs and embryos prior to expression of zygotic HSF. Second, expression from microinjected heat shock protein promoters in oocytes is induced upon heat shock. To date, however, endogenous oocyte HSF molecules have not been detected, nor has induction of HSE-binding activity been directly demonstrated. Here we report the detection of distinct stress-inducible and developmentally regulated HSE-binding activities of endogenous oocyte factors. Exposure of defolliculated oocytes to heat, cadmium, and arsenite resulted in the formation of an HSE-specific complex detectable by gel mobility shift assay. Induction of HSE-binding activity by each of these stressors corresponded to increased expression from a microinjected hsp70 promoter. The stress-inducible HSE-binding complex was recognized by antiserum against mammalian HSF1, but not by HSF2 antiserum, suggesting that aXenopushomologue of HSF1 is the major component of this activity. The HSE-binding activity of HSF1 was induced by stress treatments of stage I through VI oocytes, an indication that it is responsive to stress throughout oogenesis. During recovery from heat shock, the HSF1–HSE complex rapidly declined to control levels, but was induced for prolonged periods in oocytes exposed to continuous stress, a pattern unlike the transient activation previously observed in fertilized eggs or embryos. The kinetics of HSF1 activation in oocytes suggests that a key protein(s) regulating attenuation of the stress response is present at exceedingly low levels or is somehow modified during preembryonic development. We also detected an unusual constitutive HSE-binding complex in unstressed stage I and II oocytes, but not in later stage oocytes, eggs, developing embryos, or A6 cells. This constitutive complex was unaffected by heat or chemical treatments and was not recognized by either HSF1 or HSF2 antiserum. Appearance of the constitutive HSE-binding activity during oogenesis corresponded closely with peak levels of hsp70 mRNA detected by Northern blot analysis of RNA from staged oocytes. We suggest that the constitutive HSE-binding activity in early oocytes is formed by a unique developmentally regulated heat shock factor that may play a role in the expression of heat shock proteins during early stages of oogenesis
Targeted Mutation in β1,4-Galactosyltransferase Leads to Pituitary Insufficiency and Neonatal Lethality

AbstractDespite much attention, the function of oligosaccharide chains on glycoproteins and glycolipids remains largely unknown. Our understanding of oligosaccharide functionin vivohas been limited to the use of reagents and targeted mutations that eliminate entire classes of oligosaccharide chains. However, most biological functions for oligosaccharides have been attributed to specific terminal sequences on these glycoside chains; yet, there have been few studies that examine the consequences of modifying terminal oligosaccharide structuresin vivo.To address this issue, mice were created bearing a targeted mutation in β1,4-galactosyltransferase (GalTase), an enzyme responsible for elaboration of many of the proposed biologically active carbohydrate epitopes. Most GalTase-null mice died within the first few weeks after birth and were characterized by stunted growth, thin skin, sparse hair, and dehydration. In addition, spermatogenesis was delayed, the lungs were poorly developed, and the adrenal cortices were poorly stratified. The few surviving adults had puffy skin (myxedema) and difficulty delivering pups at birth (dystocia) and failed to lactate (agalactosis). All of these defects are consistent with endocrine insufficiency, which was confirmed by markedly decreased levels of serum thyroxine. The polyglandular nature of the endocrine insufficiency is indicative of a failure of the anterior pituitary gland to stimulate the target endocrine organs. Previousin vitrostudies have suggested that incomplete glycosylation of anterior pituitary hormones leads to the creation of hormone antagonists, which down-regulate subsequent endocrine function, producing polyglandular endocrine insufficiency. In GalTase-null mice, the anterior pituitary acquired a normal secretory phenotype during neonatal development indicative of normal glycoprotein hormone synthesis and secretion. However, as expected, the gland was devoid of GalTase activity. These results support a requirement for terminal oligosaccharide sequences for anterior pituitary hormone function. The fact that ∼10% of the GalTase-null mice survive the neonatal period indicates the presence of a previously unrecognized compensatory pathway for glycoprotein hormone glycosylation and/or action