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Masanori Taira - One of the best experts on this subject based on the ideXlab platform.
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role of crescent in convergent extension movements by modulating wnt signaling in early xenopus embryogenesis
Mechanisms of Development, 2005Co-Authors: Mikihito Shibata, Mari Itoh, Hiroki Hikasa, Sumiko Taira, Masanori TairaAbstract:Abstract The Xenopus gene crescent encodes a member of the secreted Frizzled-related protein (sFRP) family and is expressed in the head organizer region. However, the target and function of Crescent in early development are not well understood. Here, we describe a role of Crescent in the regulation of convergent extension movements (CEMs) during gastrulation and neurulation. We show that overexpression of Crescent in whole embryos or animal caps inhibits CEMs without affecting tissue specification. Consistent with this, Crescent efficiently forms complexes with Xwnt11 and Xwnt5a, in contrast to another sFRP, Frzb1. As expected, the inhibitory effect of Crescent or Xwnt11 on CEMs is cancelled when both proteins are coexpressed in the Neuroectoderm. Interestingly, when coexpressed in the dorsal mesoderm, the activity of Xwnt11 is rather enhanced by Crescent. Supporting this finding, the inhibition of CEMs by Crescent in mesodermalized but not neuralized animal caps is reversed by the dominant-negative form of Cdc42, a putative mediator of Wnt/Ca2+ pathway. Antisense morpholino oligos for Crescent impair neural plate closure and elicit microcephalic embryos with a shortened trunk without affecting early tissue specification. These data suggest a potential role for Crescent in head formation by regulating a non-canonical Wnt pathway positively in the adjacent posterior mesoderm and negatively in the overlying anterior Neuroectoderm.
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systematic screening for genes specifically expressed in the anterior Neuroectoderm during early xenopus development
The International Journal of Developmental Biology, 2005Co-Authors: Noriyuki Takahashi, Mari Itoh, Naoko Tochimoto, Shinya Ohmori, Hiroshi Mamada, Masako Inamori, Jun Shinga, Shinichi Osada, Masanori TairaAbstract:A cDNA library derived from the anterior Neuroectoderm (ANE) of Xenopus late-gastrula embryos was systematically screened to isolate novel developmental regulatory genes involved in early brain development. We isolated 1,706 5´ expressed sequence tags (ESTs), which were subdivided into 1,383 clusters and categorized into 19 classes based on predicted functions according to their similarities to other known genes. Of these, 757 clusters that were considered possible novel regulatory genes or unknown genes were subjected to expression pattern analysis using whole-mount in situ hybridization. Genes from 69 clusters (9%) were expressed in the ANE region. Based on their expression patterns and predicted amino acid sequences, 25 genes were selected for further analysis as novel Xenopus genes expressed broadly or region-specifically in the ANE. Eighteen genes were expressed in postulated patterning centers in the Neuroectoderm, including the anterior (four genes) and lateral (nine genes) neural ridges, the midbrainhindbrain boundary region (one gene) and the midline region of the neural plate (two genes), whereas 13 genes were expressed in the eye anlagen. Therefore, early regionalization of the Neuroectoderm appears to occur mainly in those neural patterning centers and the eye anlagen. We determined the entire coding regions of p54nrb, Semaphorin 6D and a novel gene designated scribble-related protein 1 (SCRP1). Interestingly, Semaphorin 6D is expressed in the mesoderm with a dorsoventral gradient, as well as in the ectoderm at the gastrula stage, implying a new role for this protein in development other than in axon guidance.
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xman1 an inner nuclear membrane protein antagonizes bmp signaling by interacting with smad1 in xenopus embryos
Development, 2003Co-Authors: Shinichi Osada, Shinya Ohmori, Masanori TairaAbstract:A family of inner nuclear membrane proteins is implicated in gene regulation by interacting with chromatin, nuclear lamina and intranuclear proteins; however, the physiological functions of these proteins are largely unknown. Using a Xenopus expression screening approach with an anterior Neuroectoderm cDNA library, we have identified an inner nuclear membrane protein, XMAN1, as a novel neuralizing factor that is encoded by the Xenopus ortholog of human MAN1. XMAN1 mRNA is expressed maternally, and appears to be restricted to the entire ectoderm at the early gastrula stage, then to the anterior Neuroectoderm at the neurula stage. XMAN1 induces anterior neural markers without mesoderm induction in ectodermal explants, and a partial secondary axis when expressed ventrally by dorsalizing the ventral mesoderm. Importantly, XMAN1 antagonizes bone morphogenetic protein (BMP) signaling downstream of its receptor Alk3, as judged by animal cap assays, in which XMAN1 blocks expression of downstream targets of BMP signaling ( Xhox3 and Msx1 ), and by luciferase reporter assays, in which XMAN1 suppresses BMP-dependent activation of the Xvent2 promoter. Deletion mutant analyses reveal that the neuralizing and BMP-antagonizing activities of XMAN1 reside in the C-terminal region, and that the C-terminal region binds to Smad1, Smad5 and Smad8, which are intracellular mediators of the BMP pathway. Interference with endogenous XMAN1 functions with antisense morpholino oligos leads to the reduction of anterior Neuroectoderm. These results provide the first evidence that the nuclear envelope protein XMAN1 acts as a Smad-interacting protein to antagonize BMP signaling during Xenopus embryogenesis.
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the xenopus receptor tyrosine kinase xror2 modulates morphogenetic movements of the axial mesoderm and Neuroectoderm via wnt signaling
Development, 2002Co-Authors: Hiroki Hikasa, Mikihito Shibata, Ichiro Hiratani, Masanori TairaAbstract:The Spemann organizer plays a central role in neural induction, patterning of the Neuroectoderm and mesoderm, and morphogenetic movements during early embryogenesis. By seeking genes whose expression is activated by the organizer-specific LIM homeobox gene Xlim-1 in Xenopus animal caps, we isolated the receptor tyrosine kinase Xror2. Xror2 is expressed initially in the dorsal marginal zone, then in the notochord and the Neuroectoderm posterior to the midbrain-hindbrain boundary. mRNA injection experiments revealed that overexpression of Xror2 inhibits convergent extension of the dorsal mesoderm and Neuroectoderm in whole embryos, as well as the elongation of animal caps treated with activin, whereas it does not appear to affect cell differentiation of neural tissue and notochord. Interestingly, mutant constructs in which the kinase domain was point-mutated or deleted (named Xror2-TM) also inhibited convergent extension, and did not counteract the wild-type, suggesting that the ectodomain of Xror2 per se has activities that may be modulated by the intracellular domain. In relation to Wnt signaling for planar cell polarity, we observed: (1) the Frizzled-like domain in the ectodomain is required for the activity of wild-type Xror2 and Xror2-TM; (2) co-expression of Xror2 with Xwnt11, Xfz7, or both, synergistically inhibits convergent extension in embryos; (3) inhibition of elongation by Xror2 in activin-treated animal caps is reversed by co-expression of a dominant negative form of Cdc42 that has been suggested to mediate the planar cell polarity pathway of Wnt; and (4) the ectodomain of Xror2 interacts with Xwnts in co-immunoprecipitation experiments. These results suggest that Xror2 cooperates with Wnts to regulate convergent extension of the axial mesoderm and Neuroectoderm by modulating the planar cell polarity pathway of Wnt.
Sang Hee Kim - One of the best experts on this subject based on the ideXlab platform.
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cns midline cells contribute to maintenance of the initial dorsoventral patterning of the drosophila ventral Neuroectoderm
Journal of Neurobiology, 2005Co-Authors: In Ok Kim, In Chul Kim, Sunmi Kim, Yeon Kyung Kwon, Pyung Lim Han, Sanghak Jeon, Sang Hee KimAbstract:Dorsoventral patterning of the Drosophila ventral Neuroectoderm is established by the expression of three evolutionarily conserved homeodomain genes: ventral nervous system defective (vnd), intermediate neuroblasts defective (ind), and muscle segment homeobox (msh) in the medial, intermediate, and lateral columns of the ventral Neuroectoderm, respectively. It was not clear whether extrinsic factor(s) from the CNS midline cells influence the initial dorsoventral patterning by controlling the expression of the dorsoventral patterning genes. We show here that the CNS midline cells, specified by single-minded (sim), are essential for maintaining expression of the dorsoventral patterning genes. Ectopic expression of sim in the ventral Neuroectoderm during the blastoderm stage repressed expression of the three homeodomain genes in the ventral Neuroectoderm. This indicates that the identity of the CNS midline cells is established by a series of repressions of the three homeodomain genes in the ventral Neuroectoderm. Ectopic expression of sim in the ventral Neuroectoderm during initial neurogenesis induced ectopic ind expression in the medial column in addition to that in the intermediate column via EGFR signaling between the ventral Neuroectoderm and midline cells. In contrast, it repressed the expression of vnd and msh in the medial and lateral columns, respectively. Our findings demonstrate that the CNS midline cells provide extrinsic positional information via EGFR signaling that maintains the initial subdivision of the ventral Neuroectoderm into three dorsoventral columns during initial neurogenesis.
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the hierarchical relationship among the spitz egfr signaling genes in cell fate determination in the drosophila ventral Neuroectoderm
Molecules and Cells, 2003Co-Authors: Jinsook Chang, Sanghak Jeon, Sang Hee KimAbstract:The spitz class and Egfr signaling (spi/Egfr) genes are required for the proper establishment of cell fate in the Drosophila ventral Neuroectoderm. We investigated the role of the central nervous system (CNS) midline cells, and the hierarchical relationship among the spi/Egfr genes, in this process by analyzing the spatial and temporal expression of several of the genes in selected spilEgfr mutants. Our analysis showed that expression of all the spilEgfr genes is severely reduced in the single-minded (sim) mutant, and ectopically induced in en-Gal4/UAS-sim embryos. This result indicates that sire acts upstream of all the other spi/Egfr genes. The CNS midline cells regulate rhomboid (rho) expression in the ventral Neuroectoderm and activate the EGFR signaling pathway. We also found that argos (aos) and orthodenticle (otd) act downstream of pointed (pnt), and that aos represses expression of otd in the lateral Neuroectoderm to establish differential cell fates in the ventral Neuroectoderm. Our findings suggest the following hierarchical relationship among the spi/Egfr genes: sim → rho, S, spi → Draf → pnt → otd.
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the cns midline cells coordinate proper cell cycle progression and identity determination of the drosophila ventral Neuroectoderm
Developmental Biology, 2000Co-Authors: Jinsook Chang, In Ok Kim, Sanghak Jeon, Jung Sook Ahn, Jae Sung Kwon, Sang Hee KimAbstract:The CNS midline cells, specified by the single-minded (sim) gene, are required for the proper patterning of the ventral CNS and epidermis, which are derived from the Drosophila ventral Neuroectoderm. Defects in the sim mutant are characterized by the loss of the gene expression, which is required for the proper formation of the ventral neurons and epidermis, and by a decrease in the spacing of longitudinal and commissural axon tracks. Molecular and cellular mechanisms for these defects were analyzed to elucidate the precise role of the CNS midline cells in proper patterning of the ventral Neuroectoderm during embryonic neurogenesis. These analyses showed that the ventral Neuroectoderm in the sim mutant fails to carry out its proper formation and characteristic cell division cycle. This resulted in the loss of the dividing Neuroectodermal cells that are located ventral to the CNS midline. The CNS midline cells are also required for the cell cycle-independent expression of the neural and epidermal markers. This indicates that the CNS midline cells are essential for the establishment and maintenance of the ventral epidermal and neuronal cell lineage by cell-cell interaction. On the other hand, the CNS midline cells do not cause extensive cell death in the ventral Neuroectoderm. This study indicates that the CNS midline cells play important roles in the coordination of the proper cell cycle progression and the correct identity determination of the adjacent ventral Neuroectoderm along the dorsoventral axis.
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the cns midline cells and spitz class genes are required for proper patterning of drosophila ventral Neuroectoderm
The International Journal of Developmental Biology, 1999Co-Authors: Chul Min Lee, Stephen T Crews, Sang Hee KimAbstract:The Drosophila embryonic central nervous system (CNS) develops from sets of neuroblasts (NBs) which segregate from the ventral Neuroectoderm during early embryogenesis. It is not well established how each individual NB in the Neuroectoderm acquires its characteristic identity along the dorsal-ventral axis. Since it is known that CNS midline cells and spitz class genes (pointed, rhomboid, single-minded, spitz and Star) are required for the proper patterning of ventral CNS and epidermis originated from the ventral Neuroectoderm, this study was carried out to determine the functional roles of the CNS midline cells and spitz class genes in the fate determination of ventral NBs and formation of mature neurons and their axon pathways. Several molecular markers for the identified NBs, neurons, and axon pathways were employed to examine marker gene expression profile, cell lineage and axon pathway formation in the spitz class mutants. This analysis showed that the CNS midline cells specified by single-minded gene as well as spitz class genes are required for identity determination of a subset of ventral NBs and for formation of mature neurons and their axon pathways. This study suggests that the CNS midline cells and spitz class genes are necessary for proper patterning of the ventral Neuroectoderm along the dorsal-ventral axis.
Lynne M Angerer - One of the best experts on this subject based on the ideXlab platform.
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integration of canonical and noncanonical wnt signaling pathways patterns the Neuroectoderm along the anterior posterior axis of sea urchin embryos
PLOS Biology, 2013Co-Authors: Ryan Range, Robert C Angerer, Lynne M AngererAbstract:Patterning the Neuroectoderm along the anterior-posterior (AP) axis is a critical event in the early development of deuterostome embryos. However, the mechanisms that regulate the specification and patterning of the Neuroectoderm are incompletely understood. Remarkably, the anterior Neuroectoderm (ANE) of the deuterostome sea urchin embryo expresses many of the same transcription factors and secreted modulators of Wnt signaling, as does the early vertebrate ANE (forebrain/eye field). Moreover, as is the case in vertebrate embryos, confining the ANE to the anterior end of the embryo requires a Wnt/β-catenin-dependent signaling mechanism. Here we use morpholino- or dominant negative-mediated interference to demonstrate that the early sea urchin embryo integrates information not only from Wnt/β-catenin but also from Wnt/Fzl5/8-JNK and Fzl1/2/7-PKC pathways to provide precise spatiotemporal control of Neuroectoderm patterning along its AP axis. Together, through the Wnt1 and Wnt8 ligands, they orchestrate a progressive posterior-to-anterior wave of re-specification that restricts the initial, ubiquitous, maternally specified, ANE regulatory state to the most anterior blastomeres. There, the Wnt receptor antagonist, Dkk1, protects this state through a negative feedback mechanism. Because these different Wnt pathways converge on the same cell fate specification process, our data suggest they may function as integrated components of an interactive Wnt signaling network. Our findings provide strong support for the idea that the sea urchin ANE regulatory state and the mechanisms that position and define its borders represent an ancient regulatory patterning system that was present in the common echinoderm/vertebrate ancestor.
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integration of canonical and noncanonical wnt signaling pathways patterns the Neuroectoderm along the anterior posterior axis of sea urchin embryos
PLOS Biology, 2013Co-Authors: Ryan Range, Robert C Angerer, Lynne M AngererAbstract:Patterning the Neuroectoderm along the anterior–posterior (AP) axis is a critical event in the early development of deuterostome embryos. However, the mechanisms that regulate the specification and patterning of the Neuroectoderm are incompletely understood. Remarkably, the anterior Neuroectoderm (ANE) of the deuterostome sea urchin embryo expresses many of the same transcription factors and secreted modulators of Wnt signaling, as does the early vertebrate ANE (forebrain/eye field). Moreover, as is the case in vertebrate embryos, confining the ANE to the anterior end of the embryo requires a Wnt/β-catenin-dependent signaling mechanism. Here we use morpholino- or dominant negative-mediated interference to demonstrate that the early sea urchin embryo integrates information not only from Wnt/β-catenin but also from Wnt/Fzl5/8-JNK and Fzl1/2/7-PKC pathways to provide precise spatiotemporal control of Neuroectoderm patterning along its AP axis. Together, through the Wnt1 and Wnt8 ligands, they orchestrate a progressive posterior-to-anterior wave of re-specification that restricts the initial, ubiquitous, maternally specified, ANE regulatory state to the most anterior blastomeres. There, the Wnt receptor antagonist, Dkk1, protects this state through a negative feedback mechanism. Because these different Wnt pathways converge on the same cell fate specification process, our data suggest they may function as integrated components of an interactive Wnt signaling network. Our findings provide strong support for the idea that the sea urchin ANE regulatory state and the mechanisms that position and define its borders represent an ancient regulatory patterning system that was present in the common echinoderm/vertebrate ancestor.
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the evolution of nervous system patterning insights from sea urchin development
Development, 2011Co-Authors: Lynne M Angerer, Shunsuke Yaguchi, Robert C Angerer, Robert D BurkeAbstract:Recent studies of the sea urchin embryo have elucidated the mechanisms that localize and pattern its nervous system. These studies have revealed the presence of two overlapping regions of neurogenic potential at the beginning of embryogenesis, each of which becomes progressively restricted by separate, yet linked, signals, including Wnt and subsequently Nodal and BMP. These signals act to specify and localize the embryonic neural fields – the anterior Neuroectoderm and the more posterior ciliary band Neuroectoderm – during development. Here, we review these conserved nervous system patterning signals and consider how the relationships between them might have changed during deuterostome evolution.
Shunsuke Yaguchi - One of the best experts on this subject based on the ideXlab platform.
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Meis transcription factor maintains the neurogenic ectoderm and regulates the anterior-posterior patterning in embryos of a sea urchin, Hemicentrotus pulcherrimus.
Developmental biology, 2018Co-Authors: Junko Yaguchi, Atsuko Yamazaki, Shunsuke YaguchiAbstract:Abstract Precise body axis formation is an essential step in the development of multicellular organisms, for most of which the molecular gradient and/or specifically biased localization of cell-fate determinants in eggs play important roles. In sea urchins, however, any biased proteins and mRNAs have not yet been identified in the egg except for vegetal cortex molecules, suggesting that sea urchin development is mostly regulated by uniformly distributed maternal molecules with contributions to axis formation that are not well characterized. Here, we describe that the maternal Meis transcription factor regulates anterior-posterior axis formation through maintenance of the most anterior territory in embryos of a sea urchin, Hemicentrotus pulcherrimus. Loss-of-function experiments revealed that Meis is intrinsically required for maintenance of the anterior Neuroectoderm specifier foxQ2 after hatching and, consequently, the morphant lost anterior Neuroectoderm characteristics. In addition, the expression patterns of univin and VEGF, the lateral ectoderm markers, and the mesenchyme-cell pattern shifted toward the anterior side in Meis morphants more than they did in control embryos, indicating that Meis contributes to the precise anteroposterior patterning by regulating the anterior Neuroectodermal fate.
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cooperative wnt nodal signals regulate the patterning of anterior Neuroectoderm
PLOS Genetics, 2016Co-Authors: Junko Yaguchi, Noriyo Takeda, Kazuo Inaba, Shunsuke YaguchiAbstract:When early canonical Wnt is experimentally inhibited, sea urchin embryos embody the concept of a Default Model in vivo because most of the ectodermal cell fates are specified as anterior Neuroectoderm. Using this model, we describe here how the combination of orthogonally functioning anteroposterior Wnt and dorsoventral Nodal signals and their targeting transcription factors, FoxQ2 and Homeobrain, regulates the precise patterning of normal Neuroectoderm, of which serotonergic neurons are differentiated only at the dorsal/lateral edge. Loss-of-function experiments revealed that ventral Nodal is required for suppressing the serotonergic neural fate in the ventral side of the Neuroectoderm through the maintenance of foxQ2 and the repression of homeobrain expression. In addition, non-canonical Wnt suppressed homeobrain in the anterior end of the Neuroectoderm, where serotonergic neurons are not differentiated. Canonical Wnt, however, suppresses foxQ2 to promote neural differentiation. Therefore, the three-dimensionally complex patterning of the Neuroectoderm is created by cooperative signals, which are essential for the formation of primary and secondary body axes during embryogenesis.
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The pre-signaling state of most of the ectoderm is neurogenic and the region is patterned along the dorsal-ventral axis after restricted anteriorly.
2016Co-Authors: Junko Yaguchi, Noriyo Takeda, Kazuo Inaba, Shunsuke YaguchiAbstract:(A) A brief summary of the early cWnt-deficient embryonic phenotype, in which the initial (default) Neuroectoderm covers most of the embryo and a number of serotonergic neurons are differentiated. In the drawings, the pink field and green spots indicate Neuroectoderm and serotonergic neurons, respectively. (B-F) foxQ2 patterns during the embryogenesis of the sea urchin, Hemicentrotus pulcherrimus. foxQ2 is initially expressed at the anterior half (B) and gradually restricted to the anterior end by the blastula/gastrula stages (C-E). (F) foxQ2 is expressed ventrally in the restricted AP region in the early pluteus stage. Left is ventral (V) and right is the dorsal (D) side. Arrowhead indicates the position where foxQ2 gene expression is missing in the AP region. (G, H) FoxQ2 is required for the development of serotonergic neurons. Without FoxQ2, serotonergic neurons are not differentiated at 48 h (H) compared to control (G). (I-L) Sagittal section of the Neuroectoderm field in a prism larva. Serotonergic neuron is differentiated at the dorsal edge of the AP and never includes FoxQ2 protein in its nucleus. Bar in (F) is 20 μm.
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the evolution of nervous system patterning insights from sea urchin development
Development, 2011Co-Authors: Lynne M Angerer, Shunsuke Yaguchi, Robert C Angerer, Robert D BurkeAbstract:Recent studies of the sea urchin embryo have elucidated the mechanisms that localize and pattern its nervous system. These studies have revealed the presence of two overlapping regions of neurogenic potential at the beginning of embryogenesis, each of which becomes progressively restricted by separate, yet linked, signals, including Wnt and subsequently Nodal and BMP. These signals act to specify and localize the embryonic neural fields – the anterior Neuroectoderm and the more posterior ciliary band Neuroectoderm – during development. Here, we review these conserved nervous system patterning signals and consider how the relationships between them might have changed during deuterostome evolution.
Shinichi Aizawa - One of the best experts on this subject based on the ideXlab platform.
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otx2 expression in anterior Neuroectoderm and forebrain midbrain is directed by more than six enhancers
Developmental Biology, 2014Co-Authors: Daisuke Kurokawa, Yusuke Sakurai, Yoko Suda, Tomomi Ohmura, Kenichi Inoue, Shinichi AizawaAbstract:Otx2 plays essential roles in each site at each step of head development. We previously identified the AN1 enhancer at 91kb 5' upstream for the Otx2 expressions in anterior Neuroectoderm (AN) at neural plate stage before E8.5, and the FM1 enhancer at 75kb 5' upstream and the FM2 enhancer at 122kb 3' downstream for the expression in forebrain/midbrain (FM) at brain vesicle stage after E8.5. The present study identified a second AN enhancer (AN2) at 88kb 5' upstream; the AN2 enhancer also recapitulates the endogenous Otx2 expression in choroid plexus, cortical hem and choroidal roof. However, the enhancer mutants indicated the presence of another AN enhancer. The study also identified a third FM enhancer (FM3) at 153kb 5' upstream. Thus, the Otx2 expressions in anterior Neuroectoderm and forebrain/midbrain are regulated by more than six enhancers located far from the coding region. The enhancers identified are differentially conserved among vertebrates; none of the AN enhancers has activities in caudal forebrain and midbrain at brain vesicle stage after E8.5, nor do any of the FM enhancers in anterior Neuroectoderm at neural plate stage before E8.5.
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evolutionary constraint on otx2 Neuroectoderm enhancers deep conservation from skate to mouse and unique divergence in teleost
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Daisuke Kurokawa, Yusuke Sakurai, Ai Inoue, Rika Nakayama, Nobuyoshi Takasaki, Yoko Suda, Tsutomu Miyake, Chris T Amemiya, Shinichi AizawaAbstract:Otx2 is a paired type homeobox gene that plays essential roles in each step and site of head development in vertebrates. In the mouse, Otx2 expression in the anterior Neuroectoderm is regulated primarily by two distinct enhancers: anterior Neuroectoderm (AN) and forebrain/midbrain (FM) enhancers at 92 kb and 75 kb 5′of the Otx2 locus, respectively. The AN enhancer has activity in the entire anterior Neuroectoderm at headfold and early somite stages, whereas the FM enhancer is subsequently active in the future caudal forebrain and midbrain ectoderm. In tetrapods, both AN and FM enhancers are conserved, whereas the AN region is missing in teleosts, despite overt Otx2 expression in the anterior Neuroectoderm. Here, we show that zebrafish and fugu FM regions drive expression not only in the forebrain and midbrain but also in the anterior Neuroectoderm at headfold stage. The analysis of coelacanth and skate genomic Otx2 orthologues suggests that the utilization of the two enhancers, AN and FM, is an ancestral condition. In contrast, the AN enhancer has been specifically lost in the teleost lineage with a compensatory establishment of AN activity within the FM enhancer. Furthermore, the AN activity in the fish FM enhancer was established by recruiting upstream factors different from those that direct the tetrapod AN enhancer, yet zebrafish FM enhancer is active in both mouse and zebrafish anterior Neuroectoderm at the headfold stage.
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ang is a novel gene expressed in early Neuroectoderm but its null mutant exhibits no obvious phenotype
Gene Expression Patterns, 2004Co-Authors: Takuya Murata, Yoko Suda, Hiroshi Kiyonari, Kenryo Furushima, Mariko Hirano, Miwa Nakamura, Shinichi AizawaAbstract:To find genes that play roles in initial regionalization of anterior Neuroectoderm, 15 novel genes were isolated that are expressed in anterior Neuroectoderm at E8.0‐E8.5. Moreover, to assess their functions by generation of mutant mice a conventional targeting strategy was designed, exploiting the availability of accurate long amplification PCR and BAC library that is coupled with genome information, in C57BL/6 strain. The ang is one of such genes; it has no known functional domains or no cognates, but is conserved not only in vertebrates, but also in Drosophila. Its expression was initially found throughout Neuroectoderm at E7.5; subsequently the expression became high in rostral brain and caudal neuropore regions and low in hindbrain and spinal cord regions. At E12.5 the expression was found in undifferentiated neuroepithelium in ventricular zone, dorsal root ganglia and several non-neural tissues. However, ang null mutant was liveborn without any apparent defects. q 2004 Elsevier B.V. All rights reserved.
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regulation of otx2 expression and its functions in mouse epiblast and anterior Neuroectoderm
Development, 2004Co-Authors: Daisuke Kurokawa, Rika Nakayama, Nobuyoshi Takasaki, Hiroshi Kiyonari, Chiharu Kimurayoshida, Isao Matsuo, Shinichi AizawaAbstract:We have identified cis-regulatory sequences acting on Otx2 expression in epiblast (EP) and anterior Neuroectoderm (AN) at about 90 kb 5′ upstream. The activity of the EP enhancer is found in the inner cell mass at E3.5 and the entire epiblast at E5.5. The AN enhancer activity is detected initially at E7.0 and ceases by E8.5; it is found later in the dorsomedial aspect of the telencephalon at E10.5. The EP enhancer includes multiple required domains over 2.3 kb, and the AN enhancer is an essential component of the EP enhancer. Mutants lacking the AN enhancer have demonstrated that these cis-sequences indeed regulate Otx2 expression in EP and AN. At the same time, our analysis indicates that another EP and AN enhancer must exist outside of the –170 kb to +120 kb range. In Otx2 ΔAN/– mutants, in which one Otx2 allele lacks the AN enhancer and the other allele is null, anteroposterior axis forms normally and anterior Neuroectoderm is normally induced. Subsequently, however, forebrain and midbrain are lost, indicating that Otx2 expression under the AN enhancer functions to maintain anterior Neuroectoderm once induced. Furthermore, Otx2 under the AN enhancer cooperates with Emx2 in diencephalon development. The AN enhancer region is conserved among mouse, human and Xenopus ; moreover, the counterpart region in Xenopus exhibited an enhancer activity in mouse anterior Neuroectoderm.