bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fgf8 and Gbx2 induction concomitant with Otx2 repression is correlated with midbrain-hindbrain fate of caudal prosencephalon
Authors: Hidalgo-Sánchez Matías , Simeone Antonio , Alvarado-Mallart Rosa-Magda 
Published: April 2021

ABSTRACT
Chick/quail transplantation experiments were performed to analyse possible factors involved in the regionalisation of the midbrain-hindbrain domain. The caudal prosomeres, expressing Otx2, were transplanted at stage HH10 into rostrocaudal levels of the midbrain-hindbrain domain, either straddling the intra-metencephalic constriction (type 1 grafts), or at rostral and medial levels of pro-rhombomere A1 (type 2 and 3 grafts, respectively); thus, in all situations, one border of the graft was in contact with the host Gbx2- and Fgf8-expressing domains. The area containing the graft, recognised by QCPN immunohistochemistry, was first analysed 48 hours after transplantation for Otx2, Gbx2, En2 and Fgf8. Although in all three situations, a large part of the graft maintained Otx2 expression, another part became Otx2 negative and was induced to express Gbx2 and Fgf8. These inductive events occurred exclusively at the interface between the Otx2-positive transplanted domain and the ipsilateral host Gbx2-positive rhombomere 1, creating a new Otx2-Gbx2 boundary within the grafted territory. In type 1 and 2 grafts, the induced Fgf8 domain is in continuity with the host Fgf8 isthmic domain, whereas for type 3 grafts, these two domains are separate. High levels of En2 expression were also induced in the area expressing Gbx2 and Fgf8, and Wnt1 and Pax2 expressions, analysed in type 3 grafts, were induced at the intragraft Otx2-Gbx2 new boundary. Moreover, at later embryonic stages, the graft developed meso-isthmo-cerebellar structures. Thus, gene expressions induced in the grafted prosencephalon not only mimicked the pattern observed in the normal midbrain-hindbrain domain, but is followed by midbrain-hindbrain cytodifferentiation, indicating that not only Fgf8 but also confrontation of Otx2 and Gbx2 may play an essential role during midbrian-hindbrain regionalisation.
Regulation of midline development by antagonism of lefty and nodal signaling
Authors: Brent W. Bisgrove , Jeffrey J. Essner , Joseph Yost H. 
Published: April 2021

ABSTRACT
The embryonic midline is crucial for the development of embryonic pattern including bilateral symmetry and left-right asymmetry. In zebrafish, lefty1 (lft1) and lefty2 (lft2) have distinct midline expression domains along the anteroposterior axis that overlap with the expression patterns of the nodal-related genes cyclops and squint. Altered expression patterns of lft1 and lft2 in zebrafish mutants that affect midline development suggests different upstream pathways regulate each expression domain. Ectopic expression analysis demonstrates that a balance of lefty and cyclops signaling is required for normal mesendoderm patterning and goosecoid, no tail and pitx2 expression. In late somite-stage embryos, lft1 and lft2 are expressed asymmetrically in the left diencephalon and left lateral plate respectively, suggesting an additional role in laterality development. A model is proposed by which the vertebrate midline, and thus bilateral symmetry, is established and maintained by antagonistic interactions among co-expressed members of the lefty and nodal subfamilies of TGF-β signaling molecules.
Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly
Authors: Wagner Kay-Uwe , Claudio Estefania , Rucker Edmund B. , Riedlinger Gregory , Broussard Christine , Schwartzberg Pamela L. , Siebenlist Ulrich , Hennighausen Lothar 
Published: April 2021

ABSTRACT
Bcl-x is a member of the Bcl2 family and has been suggested to be important for the survival and maturation of various cell types including the erythroid lineage. To define the consequences of Bcl-x loss in erythroid cells and other adult tissues, we have generated mice conditionally deficient in the Bcl-x gene using the Cre-loxP recombination system. The temporal and spatial excision of the floxed Bcl-x locus was achieved by expressing the Cre recombinase gene under control of the MMTV-LTR. By the age of five weeks, Bcl-x conditional mutant mice exhibited hyperproliferation of megakaryocytes and a decline in the number of circulating platelets. Three-month-old animals suffered from severe hemolytic anemia, hyperplasia of immature erythroid cells and profound enlargement of the spleen. We demonstrate that Bcl-x is only required for the survival of erythroid cells at the end of maturation, which includes enucleated reticulocytes in circulation. The extensive proliferation of immature erythroid cells in the spleen and bone marrow might be the result of a fast turnover of late red blood cell precursors and accelerated erythropoiesis in response to tissue hypoxia. The increase in cell death of late erythroid cells is independent from the proapoptotic factor Bax, as demonstrated in conditional double mutant mice for Bcl-x and Bax. Mice conditionally deficient in Bcl-x permitted us for the first time to study the effects of Bcl-x deficiency on cell proliferation, maturation and survival under physiological conditions in an adult animal.
Genetic and developmental bases of serial homology in vertebrate limb evolution
Authors: Ruvinsky Ilya , Gibson-Brown Jeremy J. 
Published: April 2021

ABSTRACTTwo sets of paired appendages are a characteristic feature of the body plan of jawed vertebrates. While the fossil record provides a good morphological description of limb evolution, the molecular mechanisms involved in this process are only now beginning to be understood. It is likely that the genes essential for limb development in modern vertebrates were also important players during limb evolution. In recent years, genes from a number of gene families have been described that play important roles both in limb induction and in later patterning processes. These advances facilitate inquiries into several important aspects of limb evolution such as their origin, position along the body axis, number and identity. Integrating paleontological, developmental and genetic data, we propose models to explain the evolution of paired appendages in vertebrates. Whereas previous syntheses have tended to focus on the roles of genes from a single gene family, most notably Hox genes, we emphasize the importance of considering the interactions among multiple genes from different gene families for understanding the evolution of complex developmental systems. Our models, which underscore the roles of gene duplication and regulatory ‘tinkering’, provide a conceptual framework for elucidating the evolution of serially homologous structures in general, and thus contribute to the burgeoning field seeking to uncover the genetic and developmental bases of evolution.
Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage
Authors: Malatesta Paolo , Hartfuss Eva , Götz Magdalena 
Published: April 2021

ABSTRACT
The developing central nervous system of vertebrates contains an abundant cell type designated radial glial cells. These cells are known as guiding cables for migrating neurons, while their role as precursor cells is less clear. Since radial glial cells express a variety of astroglial characteristics and differentiate as astrocytes after completing their guidance function, they have been considered as part of the glial lineage. Using fluorescence-activated cell sorting, we show here that radial glial cells also are neuronal precursors and only later, after neurogenesis, do they shift towards an exclusive generation of astrocytes. These results thus demonstrate a novel function for radial glial cells, namely their ability to generate two major cell types found in the nervous system, neurons and astrocytes.
The C. elegans Mi-2 chromatin-remodelling proteins function in vulval cell fate determination
Authors: Zelewsky Thomas von , Palladino Francesca , Brunschwig Karin , Tobler Heinz , Hajnal Alex , Müller Fritz 
Published: April 2021

ABSTRACT
The Mi-2 protein is the central component of the recently isolated NuRD nucleosome remodelling and histone deacetylase complex. Although the NuRD complex has been the subject of extensive biochemical analyses, little is known about its biological function. Here we show that the two C. elegans Mi-2 homologues, LET-418 and CHD-3, play essential roles during development. The two proteins possess both shared and unique functions during vulval cell fate determination, including antagonism of the Ras signalling pathway required for vulval cell fate induction and the proper execution of the 2° cell fate of vulval precursor cells, a process under the control of LIN-12 Notch signalling.
Two novel nodal-related genes initiate early inductive events in Xenopus Nieuwkoop center
Authors: Takahashi Shuji , Yokota Chika , Takano Kazuhiro , Tanegashima Kousuke , Onuma Yasuko , Goto Jun-Ichi , Asashima Makoto 
Published: April 2021

ABSTRACT
In vertebrates, Nodal-related protein plays crucial roles in mesoderm and endoderm induction. Here we describe two novel Xenopus nodal-related genes, Xnr5 and Xnr6, which are first zygotically expressed at the mid-blastula transition, in the dorsal-vegetal region including the Nieuwkoop center. Xnr5 and Xnr6 were isolated by expression screening of a library enriched with immediate-early-type transcripts, and are strong inducers of both mesoderm and endoderm. They also induce the other nodal-related genes in the animal cap. In embryos, cerberus-short (nodal-specific inhibitor) can inhibit Xnr1 and Xnr2 express to the same extent goosecoid, but not Xnr5 and Xnr6 transcription. Xnr5 and Xnr6 are regulated completely cell autonomously, differently from other Xnrs in the cell-dissociated embryos. The expression of Xnr5 and Xnr6 is regulated by maternal VegT and β-catenin, but does not require TGF-β signaling. Therefore, expression of Xnr5 and Xnr6 is controlled by different mechanisms from other Xnr family genes.
Lmo2 and GATA-3 associated expression in intraembryonic hemogenic sites
Authors: Manaia A. , Lemarchandel V. , Klaine M. , Max-Audit I. , Romeo P.-H. , Dieterlen-Lièvre F. , Godin I. 
Published: April 2021

ABSTRACT
It is now widely accepted that hemopoietic cells born intraembryonically are the best candidates for the seeding of definitive hemopoietic organs. To further understand the mechanisms involved in the generation of definitive hemopoietic stem cells, we analysed the expression of the hemopoietic-related transcription factors Lmo2 and GATA-3 during the early steps of mouse development (7-12 dpc), with a particular emphasis on intraembryonic hemogenic sites. We show here that both Lmo2 and GATA-3 are present in the intraembryonic regions known to give rise to hemopoietic precursors in vitro and in vivo, suggesting that they act together at key points of hemopoietic development. (1) Lmo2 and GATA-3 are expressed in the caudal mesoderm during the phase of intraembryonic precursors determination. (2) A highly transient concomitant expression is observed in the caudal intraembryonic definitive endoderm, suggesting that these factors are involved in the specification of intraembryonic hemopoietic precursors. (3) Lmo2 and GATA-3 are expressed within the hemopoietic clusters located in the aortic floor during fetal liver colonisation. Furthermore, a strong GATA-3 signal allowed us to uncover previously unreported mesodermal aggregates beneath the aorta. A combined in situ and immunocytological analysis strongly suggests that ventral mesodermal GATA-3 patches are involved in the process of intraembryonic stem cell generation.
Structure, function and evolution of sex-determining systems in Dipteran insects
Authors: Schütt Corina , Nöthiger Rolf 
Published: April 2021

ABSTRACT
Nature has evolved an astonishing variety of genetic and epigenetic sex-determining systems which all achieve the same result, the generation of two sexes. Genetic and molecular analyses, mainly performed during the last 20 years, have gradually revealed the mechanisms that govern sexual differentiation in a few model organisms. In this review, we will introduce the sex-determining system of Drosophila and compare the fruitfly to the housefly Musca domestica and other Dipteran insects. Despite the ostensible variety, all these insects use the same basic strategy: a primary genetic signal that is different in males and females, a key gene that responds to the primary signal, and a double-switch gene that eventually selects between two alternative sexual programmes. These parallels, however, do not extend to the molecular level. Except for the double-switch gene doublesex at the end of the cascade, no functional homologies were found between more distantly related insects. In particular, Sex-lethal, the key gene that controls sexual differentiation in Drosophila, does not have a sex-determining function in any other genus studied so far. These results show that sex-determining cascades, in comparison to other regulatory pathways, evolve much more rapidly.
The fax-1 nuclear hormone receptor regulates axon pathfinding and neurotransmitter expression
Authors: Much Jason W. , Slade Dennis J. , Klampert Kelly , Garriga Gian , Wightman Bruce 
Published: April 2021

ABSTRACT
Specification of neuron identity requires the activation of a number of discrete developmental programs. Among these is pathway selection by growth cones: in order for a neuron’s growth cone to respond appropriately to guidance cues presented by other cells or the extracellular matrix, the neuron must express genes to mediate the response. The fax-1 gene of C. elegans is required for pathfinding of axons that extend along the ventral nerve cord. We show that fax-1 is also required for pathfinding of axons in the nerve ring, the largest nerve bundle in the nematode, and for normal expression of FMRFamide-like neurotransmitters in the AVK interneurons. The fax-1 gene encodes a member of the superfamily of nuclear hormone receptors and has a DNA-binding domain related to the human PNR and Drosophila Tailless proteins. We observe fax-1 expression in embryonic neurons, including the AVK interneurons, just prior to axon extension, but after neurogenesis. These data suggest that fax-1 coordinately regulates the transcription of genes that function in the selection of axon pathways, neurotransmitter expression and, perhaps, other aspects of the specification of neuron identity.
mab-20 encodes Semaphorin-2a and is required to prevent ectopic cell contacts during epidermal morphogenesis in Caenorhabditis elegans
Authors: Roy Peter J. , Zheng Hong , Warren Charles E. , Culotti Joseph G. 
Published: April 2021

ABSTRACT
The Semaphorins are a family of secreted and transmembrane proteins known to elicit growth cone repulsion and collapse. We made and characterized a putative null mutant of the C. elegans gene semaphorin-2a (Ce-sema-2a). This mutant failed to complement mutants of mab-20 (Baird, S. E., Fitch, D. H., Kassem, I. A. A. and Emmons, S. W. (1991) Development 113, 515-526). In addition to low-frequency axon guidance errors, mab-20 mutants have unexpected defects in epidermal morphogenesis. Errant epidermal cell migrations affect epidermal enclosure of the embryo, body shape and sensory rays of the male tail. These phenotypic traits are explained by the formation of inappropriate contacts between cells of similar type and suggest that Ce-Sema-2a may normally prevent formation or stabilization of ectopic adhesive contacts between these cells.
The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain
Authors: Barges Stéphane , Mihaly Jozsef , Galloni Mireille , Hagstrom Kirsten , Müller Martin , Shanower Greg , Schedl Paul , Gyurkovics Henrik , Karch François 
Published: April 2021

ABSTRACT
The Drosophila bithorax complex Abdominal-B (Abd-B) gene specifies parasegmental identity at the posterior end of the fly. The specific pattern of Abd-B expression in each parasegment (PS) determines its identity and, in PS10-13, Abd-B expression is controlled by four parasegment-specific cis-regulatory domains, iab-5 to iab-8, respectively. In order to properly determine parasegmental identity, these four cis-regulatory domains must function autonomously during both the initiation and maintenance phases of BX-C regulation. The studies reported here demonstrate that the (centromere) distal end of iab-7 domain is delimited by the Fab-8 boundary. Initiators that specify PS12 identity are located on the proximal iab-7 side of Fab-8, while initiators that specify PS13 identity are located on the distal side of Fab-8, in iab-8. We use transgene assays to demonstrate that Fab-8 has enhancer blocking activity and that it can insulate reporter constructs from the regulatory action of the iab-7 and iab-8 initiators. We also show that the Fab-8 boundary defines the realm of action of a nearby iab-8 Polycomb Response Element, preventing this element from ectopically silencing the adjacent domain. Finally, we demonstrate that the insulating activity of the Fab-8 boundary in BX-C is absolutely essential for the proper specification of parasegmental identity by the iab-7 and iab-8 cis-regulatory domains. Fab-8 together with the previously identified Fab-7 boundary delimit the first genetically defined higher order domain in a multicellular eukaryote.
Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm
Authors: Kishi Masashi , Mizuseki Kenji , Sasai Noriaki , Yamazaki Hiroshi , Shiota Kohei , Nakanishi Shigetada , Sasai Yoshiki 
Published: April 2021

ABSTRACT
From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expressed in neural tissues and sensory epithelia. In this report, we show that Sox2 function is required for neural differentiation of early Xenopus ectoderm. Microinjection of dominant-negative forms of Sox2 (dnSox2) mRNA inhibits neural differentiation of animal caps caused by attenuation of BMP signals. Expression of dnSox2 in developing embryos suppresses expression of N-CAM and regional neural markers. We have analyzed temporal requirement of Sox2-mediated signaling by using an inducible dnSox2 construct fused to the ligand-binding domain of the glucocorticoid receptor. Attenuation of Sox2 function both from the late blastula stage and from the late gastrula stage onwards causes an inhibition of neural differentiation in animal caps and in whole embryos. Additionally, dnSox2-injected cells that fail to differentiate into neural tissues are not able to adopt epidermal cell fate. These data suggest that Sox2-class genes are essential for early neuroectoderm cells to consolidate their neural identity during secondary steps of neural differentiation.
The Arabidopsis embryonic shoot fate map
Authors: Woodrick Robert , Martin Paula R. , Birman Ilya , Pickett F. Bryan 
Published: April 2021

ABSTRACT
A fate map has been constructed for the shoot apical region of the embryo of the dicotyledonous plant Arabidopsis thaliana using spontaneously arising clonal albino sectors caused by the chloroplast mutator 1-2 mutation. Chimeric seedlings exhibiting albino sectors shared between the cotyledons and first true leaves revealed patterns of organ inclusion and exclusion. Frequencies of clone sharing were used to calculate developmental distances between organs based on the frequency of clonal sectors failing to extend between different organs. The resulting fate map shows asymmetry in the developmental distances between the cotyledons (embryonic leaves) which in turn predicts the location of the first post-germination leaf and the handedness of the spiral of leaf placement around the central stem axis in later development. The map suggests that embryonic leaf fate specification in the cotyledons may represent a developmental ground state necessary for the formation of the shoot apical meristem.
Combined activities of Gurken and Decapentaplegic specify dorsal chorion structures of the Drosophila egg
Authors: Peri Francesca , Roth Siegfried 
Published: April 2021

ABSTRACT
During Drosophila oogenesis Gurken, associated with the oocyte nucleus, activates the Drosophila EGF receptor in the follicular epithelium. Gurken first specifies posterior follicle cells, which in turn signal back to the oocyte to induce the migration of the oocyte nucleus from a posterior to an anterior-dorsal position. Here, Gurken signals again to specify dorsal follicle cells, which give rise to dorsal chorion structures including the dorsal appendages. If Gurken signaling is delayed and starts after stage 6 of oogenesis the nucleus remains at the posterior pole of the oocyte. Eggs develop with a posterior ring of dorsal appendage material that is produced by main-body follicle cells expressing the gene Broad-Complex. They encircle terminal follicle cells expressing variable amounts of the TGFβ homologue, decapentaplegic. By ectopically expressing decapentaplegic and clonal analysis with Mothers against dpp we show that Decapentaplegic signaling is required for Broad-Complex expression. Thus, the specification and positioning of dorsal appendages along the anterior-posterior axis depends on the intersection of both Gurken and Decapentaplegic signaling. This intersection also induces rhomboid expression and thereby initiates the positive feedback loop of EGF receptor activation, which positions the dorsal appendages along the dorsal-ventral egg axis.
The growth of the dermomyotome and formation of early myotome lineages in thoracolumbar somites of chicken embryos
Authors: Denetclaw Wilfred F. , Ordahl Charles P. 
Published: April 2021

ABSTRACT
Myotome formation in the epaxial and hypaxial domains of thoraco-lumbar somites was analyzed using fluorescent vital dye labeling of dermomyotome cells and cell-fate assessment by confocal microscopy. Muscle precursor cells for the epaxial and hypaxial myotomes are predominantly located in the dorsomedial and ventrolateral dermomyotome lips, respectively, and expansion of the dermomyotome is greatest along its mediolateral axis coincident with the dorsalward and ventralward growth directions of the epaxial and hypaxial myotomes. Measurements of the dermomyotome at different stages of development shows that myotome growth begins earlier in the epaxial than in the hypaxial domain, but that after an initial lag phase, both progress at the same rate. A combination of dye injection and/or antibody labeling of early and late-expressed muscle contractile proteins confirms the myotome mediolateral growth directions, and shows that the myotome thickness increases in a superficial (near dermis) to deep (near sclerotome) growth direction. These findings also provide a basis for predicting the following gene expression sequence program for the earliest muscle precursor lineages in mouse embryos: Pax-3 (stem cells), myf-5 (myoblast cells) and myoD (myocytes). The movements and mitotic activity of early muscle precursor cells lead to the conclusion that patterning and growth in the myotome specifically, and in the epaxial and hypaxial domains of the body generally, are governed by morphogenetic cell movements.