bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presenilin-1 regulates neuronal differentiation during neurogenesis
Authors: Handler Melissa , Yang Xudong , Shent Jie 
Published: April 2021

ABSTRACT
Mutations in Presenilin-1 (PSP) are a major cause of familial Alzheimer’s disease. Our previous studies showed that PS1 is required for murine neural development. Here we report that lack of PS1 leads to premature differentiation of neural progenitor cells, indicating a role for PS1 in a cell fate decision between postmitotic neurons and neural progenitor cells. Neural proliferation and apoptotic cell death during neurogenesis are unaltered in PS1−/− mice, suggesting that the reduction in the neural progenitor cells observed in the PS1−/− brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In addition, the premature neuronal differentiation in the PS1−/− brain is associated with aberrant neuronal migration and disorganization of the laminar architecture of the developing cerebral hemisphere. In the ventricular zone of PS1−/− mice, expression of the Notch1 downstream effector gene Hes5 is reduced and expression of the Notch1 ligand Dll1 is elevated, whereas expression of Notch1 is unchanged. The level of Dll1 transcripts is also increased in the presomitic mesoderm of PS1−/− embryos, while the level of Notch1 transcripts is unchanged, in contrast to a previous report (Wong et al., 1997, Nature 387, 288-292). These results provide direct evidence that PS1 controls neuronal differentiation in association with the downregulation of Notch signalling during neurogenesis.
Blastocyst H2 receptor is the target for uterine histamine in implantation in the mouse
Authors: Zhao Xuemei , Ma Wen-ge , Das Sanjoy K. , Dey Sudhansu K. , Paria Bibhash C. 
Published: April 2021

ABSTRACT
The process of implantation is a ‘two-way’ interaction between the blastocyst and uterus. It has long been suspected that histamine is an important mediator in embryo-uterine interactions during implantation, but its source, targets and mechanism of actions remained undefined. We have recently demonstrated that uterine epithelial cells are the source of histamine, which peaks on day 4 of pregnancy (the day of implantation) in the mouse. In searching for its target and site of action, we discovered that preimplantation blastocysts, which express histamine type 2 receptor (H2), is the target for histamine action. Using multiple approaches, we demonstrate herein that uterine-derived histamine interacts with embryonic H2 receptors in a paracrine fashion to initiate the process of implantation.
Hedgehog signals regulate multiple aspects of gastrointestinal development
Authors: Ramalho-Santos Miguel , Melton Douglas A. , McMahon Andrew P. 
Published: April 2021

ABSTRACT
The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells of mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis of the gut and its derivatives. We have assessed the function of Sonic hedgehog and Indian hedgehog genes, which encode members of the Hedgehog family of cell signals. Both are expressed in gut endoderm, whereas target genes are expressed in discrete layers in the mesenchyme. It was unclear whether functional redundancy between the two genes would preclude a genetic analysis of the roles of Hedgehog signaling in the mouse gut. We show here that the mouse gut has both common and separate requirements for Sonic hedgehog and Indian hedgehog. Both Sonic hedgehog and Indian hedgehog mutant mice show reduced smooth muscle, gut malrotation and annular pancreas. Sonic hedgehog mutants display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutants show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung’s disease (aganglionic colon). These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations.
Misexpression of basic helix-loop-helix genes in the murine cerebral cortex affects cell fate choices and neuronal survival
Authors: Cai Li , Morrow Eric M. , Cepko Constance L. 
Published: April 2021

ABSTRACTTo investigate the role(s) of basic helix-loop-helix genes (bHLH) genes in the developing murine cerebral cortex, Mash1, Math2, Math3, Neurogenin1 (Ngn1), Ngn2, NeuroD, NeuroD2 and Id1 were transduced in vivo into the embryonic and postnatal cerebral cortex using retrovirus vectors. The morphology and location of infected cells were analyzed at postnatal stages. The data indicate that a subset of bHLH genes are capable of regulating the choice of neuronal versus glial fate and that, when misexpressed, they can be deleterious to the survival of differentiating neurons, but not glia.
Temporal regulation of Apterous activity during development of the Drosophila wing
Authors: Milán Marco , Cohen Stephen M. 
Published: April 2021

ABSTRACT
Dorsoventral axis formation in the Drosophila wing depends on the activity of the selector gene apterous. Although selector genes are usually thought of as binary developmental switches, we find that Apterous activity is negatively regulated during wing development by its target gene dLMO. Apterous-dependent expression of Serrate and fringe in dorsal cells leads to the restricted activation of Notch along the dorsoventral compartment boundary. We present evidence that the ability of cells to participate in this Apterous-dependent cell-interaction is under spatial and temporal control. Apterous-dependent expression of dLMO causes downregulation of Serrate and fringe and allows expression of Delta in dorsal cells. This limits the time window during which dorsoventral cell interactions can lead to localized activation of Notch and induction of the dorsoventral organizer. Overactivation of Apterous in the absence of dLMO leads to overexpression of Serrate, reduced expression of Delta and concomitant defects in differentiation and cell survival in the wing primordium. Thus, downregulation of Apterous activity is needed to allow normal wing development.
Restricted patterning of vestigial expression in Drosophila wing imaginal discs requires synergistic activation by both Mad and the Drifter POU domain transcription factor
Authors: Certel Kaan , Hudson Angela , Carroll Sean B. , Johnson Wayne A. 
Published: April 2021

ABSTRACT
The Drosophila Vestigial protein has been shown to play an essential role in the regulation of cell proliferation and differentiation within the developing wing imaginal disc. Cell-specific expression of vg is controlled by two separate transcriptional enhancers. The boundary enhancer controls expression in cells near the dorsoventral (DV) boundary and is regulated by the Notch signal transduction pathway, while the quadrant enhancer responds to the Decapentaplegic and Wingless morphogen gradients emanating from cells near the anteroposterior (AP) and DV boundaries, respectively. MAD-dependent activation of the vestigial quadrant enhancer results in broad expression throughout the wing pouch but is excluded from cells near the DV boundary. This has previously been thought to be due to direct repression by a signal from the DV boundary; however, we show that this exclusion of quadrant enhancer-dependent expression from the DV boundary is due to the absence of an additional essential activator in those cells. The Drosophila POU domain transcriptional regulator, Drifter, is expressed in all cells within the wing pouch expressing a vgQ-lacZ transgene and is also excluded from the DV boundary. Viable drifter hypomorphic mutations cause defects in cell proliferation and wing vein patterning correlated with decreased quadrant enhancer-dependent expression. Drifter misexpression at the DV boundary using the GAL4/UAS system causes ectopic outgrowths at the distal wing tip due to induction of aberrant Vestigial expression, while a dominant-negative Drifter isoform represses expression of vgQ-lacZ and causes severe notching of the adult wing. In addition, we have identified an essential evolutionarily conserved sequence element bound by the Drifter protein with high affinity and located adjacent to the MAD binding site within the quadrant enhancer. Our results demonstrate that Drifter functions along with MAD as a direct activator of Vestigial expression in the wing pouch.
Sperm extract injection into ascidian eggs signals Ca2+ release by the same pathway as fertilization
Authors: Runft Linda L. , Jaffe Laurinda A. 
Published: April 2021

ABSTRACT
Injection of eggs of various species with an extract of sperm cytoplasm stimulates intracellular Ca2+ release that is spatially and temporally like that occurring at fertilization, suggesting that Ca2+release at fertilization may be initiated by a soluble factor from the sperm. Here we investigate whether the signalling pathway that leads to Ca2+release in response to sperm extract injection requires the same signal transduction molecules as are required at fertilization. Eggs of the ascidian Ciona intestinalis were injected with the Src-homology 2 domains of phospholipase Cγ or of the Src family kinase Fyn (which act as specific dominant negative inhibitors of the activation of these enzymes), and the effects on Ca2+release at fertilization or in response to injection of a sperm extract were compared. Our findings indicate that both fertilization and sperm extract injection initiate Ca2+release by a pathway requiring phospholipase Cγ and a Src family kinase. These results support the hypothesis that, in ascidians, a soluble factor from the sperm cytoplasm initiates Ca2+release at fertilization, and indicate that the activating factor from the sperm may be a regulator, directly or indirectly, of a Src family kinase in the egg.
The eli1 mutation reveals a link between cell expansion and secondary cell wall formation in Arabidopsis thaliana
Authors: Caño-Delgado Ana I. , Metzlaff Karin , Bevan Michael W. 
Published: April 2021

ABSTRACT
Mutants with altered patterns of lignification have been identified in a population of mutagenised Arabidopsis seedlings. One of the mutants exhibited ectopic lignification (eli) of cells throughout the plant that never normally lignify. The reduced expansion of eli1 cells resulted in a stunted phenotype, and xylem cells were misshapen and failed to differentiate into continuous strands, causing a disorganized xylem. Analysis of phenotypes associated with double mutants of eli1 lit (lion’s tail), a cell expansion mutant, indicated that the primary defect in eli1 plants may be inappropriate initiation of secondary wall formation and subsequent aberrant lignification of cells caused by altered cell expansion. Related ectopic lignification phenotypes were also observed in other cell expansion mutants, suggesting a mechanism that senses cell size and controls subsequent secondary wall formation. Interactions between eli1 and wol (woodenleg), a mutant altering xylem cell specification, revealed a role for ELI1 in promoting formation of continuous xylem strands, and demonstrated that ELI1 functions during cell elongation zone in the primary root and other tissues.
Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary
Authors: Smith Devyn M. , Nielsen Corinne , Tabin Clifford J. , Roberts Drucilla J. 
Published: April 2021

ABSTRACT
Patterning of the gut into morphologically distinct regions results from the appropriate factors being expressed in strict spatial and temporal patterns to assign cells their fates in development. Often, the boundaries of gene expression early in development correspond to delineations between different regions of the adult gut. For example, Bmp4 is expressed throughout the hindgut and midgut, but is not expressed in the early gizzard. Ectopic BMP4 in the gizzard caused a thinning of the muscularis. To understand this phenotype we examined the expression of the receptors transducing BMP signaling during gut development. We find that the BMP receptors are differentially expressed in distinct regions of the chicken embryonic gut. By using constitutively activated versions of the BMP type I receptors, we find that the BMP receptors act similarly to BMP4 in the gizzard when ectopically expressed. We show that the mesodermal thinning seen upon ectopic BMP signaling is due to an increase in apoptosis and a decrease in proliferation within the gizzard mesoderm. The mesodermal thinning is characterized by a disorganization and lack of differentiation of smooth muscle in the gizzard mesoderm. Further, ectopic BMP receptors cause an upregulation of Nkx2.5, the pyloric sphincter marker, similar to that seen with ectopic BMP4. This upregulation of Nkx2.5 is a cell-autonomous event within the mesoderm of the gizzard. We also find that Nkx2.5 is necessary and sufficient for establishing aspects of pyloric sphincter differentiation.
decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm
Authors: Yang Xiang , Beest Moniek van , Clevers Hans , Jones Tamara , Hursh Deborah A. , Mortin Mark A. 
Published: April 2021

ABSTRACT
Drosophila T cell factor (dTcf) mediates transcriptional activation in the presence of Wingless signalling and repression in its absence. Wingless signalling is required for the correct expression of decapentaplegic (dpp), a Transforming Growth Factor β family member, in parasegments 3 and 7 of the Drosophila visceral mesoderm. Here we demonstrate that a dpp enhancer element, which directs expression of a reporter gene in the visceral mesoderm in a pattern indistinguishable from dpp, has two functional dTcf binding sites. Mutations that reduce or eliminate Wingless signalling abolish dpp reporter gene expression in parasegment 3 and reduce it in parasegment 7 while ectopic expression of Wingless signalling components expand reporter gene expression anteriorly in the visceral mesoderm. However, mutation of the dTcf binding sites in the dpp enhancer results in ectopic expression of reporter gene expression throughout the visceral mesoderm, with no diminution of expression in the endogenous sites of expression. These results demonstrate that the primary function of dTcf binding to the dpp enhancer is repression throughout the visceral mesoderm and that activation by Wingless signalling is probably not mediated via these dTcf binding sites to facilitate correct dpp expression in the visceral mesoderm.
Wnt/β-catenin signaling regulates the expression of the homeobox gene Cdx1 in embryonic intestine
Authors: Lickert Heiko , Domon Claire , Huls Gerwin , Wehrle Christian , Duluc Isabelle , Clevers Hans , Meyer Barbara I. , Freund Jean-Noel , Kemler Rolf 
Published: April 2021

ABSTRACT
During mammalian development, the Cdx1 homeobox gene exhibits an early period of expression when the embryonic body axis is established, and a later period where expression is restricted to the embryonic intestinal endoderm. Cdx1 expression is maintained throughout adulthood in the proliferative cell compartment of the continuously renewed intestinal epithelium, the crypts. In this study, we provide evidence in vitro and in vivo that Cdx1 is a direct transcriptional target of the Wnt/β-catenin signaling pathway. Upon Wnt stimulation, expression of Cdx1 can be induced in mouse embryonic stem (ES) cells as well as in undifferentiated rat embryonic endoderm. Tcf4-deficient mouse embryos show abrogation of Cdx1 protein in the small intestinal epithelium, making Tcf4 the likely candidate to transduce Wnt signal in this part of gut. The promoter region of the Cdx1 gene contains several Tcf-binding motifs, and these bind Tcf/Lef1/β-catenin complexes and mediate β-catenin-dependent transactivation. The transcriptional regulation of the homeobox gene Cdx1 in the intestinal epithelium by Wnt/β-catenin signaling underlines the importance of this signaling pathway in mammalian endoderm development.
Auxin and ETTIN in Arabidopsis gynoecium morphogenesis
Authors: Nemhauser Jennifer L. , Feldman Lewis J. , Zambryski Patricia C. 
Published: April 2021

ABSTRACT
The phytohormone auxin has wide-ranging effects on growth and development. Genetic and physiological approaches implicate auxin flux in determination of floral organ number and patterning. This study uses a novel technique of transiently applying a polar auxin transport inhibitor, N-1-naphthylphthalamic acid (NPA), to developing Arabidopsis flowers to further characterize the role of auxin in organogenesis. NPA has marked effects on floral organ number as well as on regional specification in wild-type gynoecia, as defined by morphological and histological landmarks for regional boundaries, as well as tissue-specific reporter lines. NPA’s effects on gynoecium patterning mimic the phenotype of mutations in ETTIN, a member of the auxin response factor family of transcription factors. In addition, application of different concentrations of NPA reveal an increased sensitivity of weak ettin alleles to disruptions in polar auxin transport. In contrast, the defects found in spatula gynoecia are partially rescued by treatment with NPA. A model is proposed suggesting an apical-basal gradient of auxin during gynoecium development. This model provides a mechanism linking ETTIN’s putative transcriptional regulation of auxin-responsive genes to the establishment or elaboration of tissue patterning during gynoecial development.
Maternally controlled β-catenin-mediated signaling is required for organizer formation in the zebrafish
Authors: Kelly Christina , Chin Alvin J. , Leatherman, Judith L. , and David J. Kozlowski , Weinberg Eric S. 
Published: April 2021

ABSTRACT
We have identified and characterized a zebrafish recessive maternal effect mutant, ichabod, that results in severe anterior and dorsal defects during early development. The ichabod mutation is almost completely penetrant, but exhibits variable expressivity. All mutant embryos fail to form a normal embryonic shield; most fail to form a head and notochord and have excessive development of ventral tail fin tissue and blood. Abnormal dorsal patterning can first be observed at 3.5 hpf by the lack of nuclear accumulation of β-catenin in the dorsal yolk syncytial layer, which also fails to express bozozok/dharma/nieuwkoid and znr2/ndr1/squint. At the onset of gastrulation, deficiencies in expression of dorsal markers and expansion of expression of markers of ventral tissues indicate a dramatic alteration of dorsoventral identity. Injection of β-catenin RNA markedly dorsalized ichabod embryos and often completely rescued the phenotype, but no measurable dorsalization was obtained with RNAs encoding upstream Wnt pathway components. In contrast, dorsalization was obtained when RNAs encoding either Bozozok/Dharma/ Nieuwkoid or Znr2/Ndr1/Squint were injected. Moreover, injection of β-catenin RNA into ichabod embryos resulted in activation of expression of these two genes, which could also activate each other. RNA injection experiments strongly suggest that the component affected by the ichabod mutation acts on a step affecting β-catenin nuclear localization that is independent of regulation of β-catenin stability. This work demonstrates that a maternal gene controlling localization of β-catenin in dorsal nuclei is necessary for dorsal yolk syncytial layer gene activity and formation of the organizer in the zebrafish.
NOZZLE regulates proximal-distal pattern formation, cell proliferation and early sporogenesis during ovule development in Arabidopsis thaliana
Authors: Balasubramanian Sureshkumar , Schneitz Kay 
Published: April 2021

ABSTRACT
With the characterisation of the NOZZLE gene we aim at a better understanding of the molecular and genetic mechanism underlying pattern formation and growth control during floral organogenesis. Our data indicate that NOZZLE links these processes during ovule development. In the ovule primordium NOZZLE plays a central role in the formation of the nucellus through antagonizing the activities of BELL, AINTEGUMENTA and INNER NO OUTER, all encoding putative transcription factors, in the prospective nucellar region. We provide evidence that NOZZLE and BELL are chalaza identity genes that share overlapping functions in establishing the prospective chalaza of the ovule. In addition, NOZZLE plays a role in controlling the cell number and by this means the length of the funiculus, again through antagonizing AINTEGUMENTA and INNER NO OUTER function. NOZZLE is also required for the development of the integuments. We show that during the initial phase of this process NOZZLE is transcriptionally regulated by AINTEGUMENTA and INNER NO OUTER. NOZZLE thus represents a downstream target of these two genes in the integument development pathway.
The C. elegans NeuroD homolog cnd-1 functions in multiple aspects of motor neuron fate specification
Authors: Hallam Steven , Singer Emily , Waring David , Jin Yishi 
Published: April 2021

ABSTRACT
The basic helix-loop-helix transcription factor NeuroD (Neurod1) has been implicated in neuronal fate determination, differentiation and survival. Here we report the expression and functional analysis of cnd-1, a C. elegans NeuroD homolog. cnd-1 expression was first detected in neuroblasts of the AB lineage in 14 cell embryos and maintained in many neuronal descendants of the AB lineage during embryogenesis, diminishing in most terminally differentiated neurons prior to hatching. Specifically, cnd-1 reporter genes were expressed in the precursors of the embryonic ventral cord motor neurons and their progeny. A loss-of-function mutant, cnd-1(ju29), exhibited multiple defects in the ventral cord motor neurons. First, the number of motor neurons was reduced, possibly caused by the premature withdrawal of the precursors from mitotic cycles. Second, the strict correlation between the fate of a motor neuron with respect to its lineage and position in the ventral cord was disrupted, as manifested by the variable expression pattern of motor neuron fate specific markers. Third, motor neurons also exhibited defects in terminal differentiation characteristics including axonal morphology and synaptic connectivity. Finally, the expression patterns of three neuronal type-specific transcription factors, unc-3, unc-4 and unc-30, were altered. Our data suggest that cnd-1 may specify the identity of ventral cord motor neurons both by maintaining the mitotic competence of their precursors and by modulating the expression of neuronal type-specific determination factors. cnd-1 appears to have combined the functions of several vertebrate neurogenic bHLH proteins and may represent an ancestral form of this protein family.