XB-ART-39749
Dev Biol
May 1, 2009;
329
(1):
80-95.
foxD5 plays a critical upstream role in regulating neural ectodermal fate and the onset of neural differentiation.
Abstract
foxD5 is expressed in the nascent neural ectoderm concomitant with several other neural-fate specifying transcription factors. We used loss-of-function and gain-of-function approaches to analyze the functional position of foxD5 amongst these other factors. Loss of FoxD5 reduces the expression of sox2, sox11, soxD, zic1, zic3 and Xiro1-3 at the onset of gastrulation, and of geminin, sox3 and zic2, which are maternally expressed, by late gastrulation. At neural plate stages most of these genes remain reduced, but the domains of zic1 and zic3 are expanded. Increased FoxD5 induces geminin and zic2, weakly represses sox11 at early gastrula but later (st12) induces it; weakly represses sox2 and sox3 transiently and strongly represses soxD, zic1, zic3 and Xiro1-3. The foxD5 effects on zic1, zic3 and Xiro1-3 involve transcriptional repression, whereas those on geminin and zic2 involve transcriptional activation. foxD5''s effects on geminin, sox11 and zic2 occur at the onset of gastrulation, whereas the other genes require earlier foxD5 activity. geminin, sox11 and zic2, each of which is up-regulated directly by foxD5, are all required to account for foxD5 phenotypes, indicating that this triad constitutes a transcriptional network rather than linear path that coordinately up-regulates genes that promote an immature neural fate and inhibits genes that promote the onset of neural differentiation. We also show that foxD5 promotes an ectopic neural fate in the epidermis by reducing BMP signaling. Several of the genes that are repressed by foxD5 in turn reduce foxD5 expression, contributing to the medial-lateral patterning of the neural plate.
PubMed ID: 19250931
PMC ID: PMC2672197
Article link: Dev Biol
Grant support: [+]
NS23158 NINDS NIH HHS , R01 NS023158-15 NINDS NIH HHS , R01 NS023158-15S1 NINDS NIH HHS , R01 NS023158-16 NINDS NIH HHS , R01 NS023158-17 NINDS NIH HHS , R01 NS023158-18 NINDS NIH HHS , R01 NS023158-19A1 NINDS NIH HHS , R01 NS023158-20 NINDS NIH HHS , R01 NS023158-20S1 NINDS NIH HHS , R01 NS023158-20S2 NINDS NIH HHS , R01 NS023158-21 NINDS NIH HHS , R01 NS023158-22 NINDS NIH HHS , R01 NS023158 NINDS NIH HHS
Species referenced: Xenopus laevis
Genes referenced: acss2.2 foxd4l1.1 gal.2 gem gmnn irx1 irx2 irx3 klf6 krt12.4 myc sox11 sox15 sox2 sox3 st13 st14 szl tfap2a zic1 zic2 zic3
Antibodies: Smad1 Ab7
Morpholinos: foxd4l1.1 MO1 foxd4l1.2 MO1
Article Images: [+] show captions
References [+] :
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Wegner, From head to toes: the multiple facets of Sox proteins. 1999, Pubmed
Wegner, From stem cells to neurons and glia: a Soxist's view of neural development. 2005, Pubmed
Wijchers, In control of biology: of mice, men and Foxes. 2006, Pubmed
Yaklichkin, Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators. 2007, Pubmed
Yang, Beta-catenin/Tcf-regulated transcription prior to the midblastula transition. 2002, Pubmed , Xenbase
Zappone, Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. 2000, Pubmed
de Graaf, Hormone-inducible expression of secreted factors in zebrafish embryos. 1999, Pubmed
de la Calle-Mustienes, Xiro homeoproteins coordinate cell cycle exit and primary neuron formation by upregulating neuronal-fate repressors and downregulating the cell-cycle inhibitor XGadd45-gamma. 2002, Pubmed , Xenbase
Bani-Yaghoub, Role of Sox2 in the development of the mouse neocortex. 2006, Pubmed
Bellefroid, Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification. 1998, Pubmed , Xenbase
Bergsland, The establishment of neuronal properties is controlled by Sox4 and Sox11. 2006, Pubmed
Brewster, Gli/Zic factors pattern the neural plate by defining domains of cell differentiation. 1998, Pubmed , Xenbase
Bylund, Vertebrate neurogenesis is counteracted by Sox1-3 activity. 2003, Pubmed
Carlsson, Forkhead transcription factors: key players in development and metabolism. 2002, Pubmed
De Robertis, Dorsal-ventral patterning and neural induction in Xenopus embryos. 2004, Pubmed , Xenbase
Ellis, SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult. 2005, Pubmed
Faure, Endogenous patterns of TGFbeta superfamily signaling during early Xenopus development. 2000, Pubmed , Xenbase
Fetka, Neuroectodermal specification and regionalization of the Spemann organizer in Xenopus. 2000, Pubmed , Xenbase
Glavic, Xiro-1 controls mesoderm patterning by repressing bmp-4 expression in the Spemann organizer. 2001, Pubmed , Xenbase
Gomez-Skarmeta, Araucan and caupolican, two members of the novel iroquois complex, encode homeoproteins that control proneural and vein-forming genes. 1996, Pubmed
Graham, SOX2 functions to maintain neural progenitor identity. 2003, Pubmed
Gómez-Skarmeta, The Wnt-activated Xiro1 gene encodes a repressor that is essential for neural development and downregulates Bmp4. 2001, Pubmed , Xenbase
Gómez-Skarmeta, Xiro, a Xenopus homolog of the Drosophila Iroquois complex genes, controls development at the neural plate. 1998, Pubmed , Xenbase
Hiraoka, XLS13A and XLS13B: SRY-related genes of Xenopus laevis. 1997, Pubmed , Xenbase
Hollenberg, Use of a conditional MyoD transcription factor in studies of MyoD trans-activation and muscle determination. 1993, Pubmed
Huang, Asymmetrical blastomere origin and spatial domains of dopamine and neuropeptide Y amacrine subtypes in Xenopus tadpole retina. 1996, Pubmed , Xenbase
Huang, Noggin signaling from Xenopus animal blastomere lineages promotes a neural fate in neighboring vegetal blastomere lineages. 2006, Pubmed , Xenbase
Hutcheson, The bHLH factors Xath5 and XNeuroD can upregulate the expression of XBrn3d, a POU-homeodomain transcription factor. 2001, Pubmed , Xenbase
Hyodo-Miura, Involvement of NLK and Sox11 in neural induction in Xenopus development. 2002, Pubmed , Xenbase
Inoue, Zic1 and Zic3 regulate medial forebrain development through expansion of neuronal progenitors. 2007, Pubmed
Kaestner, The mouse fkh-2 gene. Implications for notochord, foregut, and midbrain regionalization. 1996, Pubmed
Kato, Neuralization of the Xenopus embryo by inhibition of p300/ CREB-binding protein function. 1999, Pubmed , Xenbase
Katoh, Human FOX gene family (Review). 2004, Pubmed
Kishi, Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm. 2000, Pubmed , Xenbase
Kolm, Efficient hormone-inducible protein function in Xenopus laevis. 1995, Pubmed , Xenbase
Kroll, Geminin in embryonic development: coordinating transcription and the cell cycle during differentiation. 2006, Pubmed , Xenbase
Kroll, Geminin, a neuralizing molecule that demarcates the future neural plate at the onset of gastrulation. 1998, Pubmed , Xenbase
Kuo, Opl: a zinc finger protein that regulates neural determination and patterning in Xenopus. 1998, Pubmed , Xenbase
Kuroda, Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, beta-Catenin, and Cerberus. 2004, Pubmed , Xenbase
Kurth, Establishment of mesodermal gene expression patterns in early Xenopus embryos: the role of repression. 2005, Pubmed , Xenbase
Lee, Embryonic dorsal-ventral signaling: secreted frizzled-related proteins as inhibitors of tolloid proteinases. 2006, Pubmed , Xenbase
Levine, Proposal of a model of mammalian neural induction. 2007, Pubmed
Levine, Gene regulatory networks for development. 2005, Pubmed
Li, Generation of purified neural precursors from embryonic stem cells by lineage selection. 1998, Pubmed
Luo, The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions. 2004, Pubmed
Mattioni, Regulation of protein activities by fusion to steroid binding domains. 1995, Pubmed
Mizuseki, Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction. 1998, Pubmed , Xenbase
Mizuseki, SoxD: an essential mediator of induction of anterior neural tissues in Xenopus embryos. 1998, Pubmed , Xenbase
Moody, Fates of the blastomeres of the 16-cell stage Xenopus embryo. 1987, Pubmed , Xenbase
Moody, Cell lineage analysis in Xenopus embryos. 2000, Pubmed , Xenbase
Moody, Neural induction, neural fate stabilization, and neural stem cells. 2003, Pubmed
Nakata, Xenopus Zic3, a primary regulator both in neural and neural crest development. 1997, Pubmed , Xenbase
Nakata, Xenopus Zic family and its role in neural and neural crest development. 1999, Pubmed , Xenbase
Niehrs, Mesodermal patterning by a gradient of the vertebrate homeobox gene goosecoid. 1994, Pubmed , Xenbase
Papanayotou, A mechanism regulating the onset of Sox2 expression in the embryonic neural plate. 2008, Pubmed
Penzel, Characterization and early embryonic expression of a neural specific transcription factor xSOX3 in Xenopus laevis. 1998, Pubmed , Xenbase
Pitulescu, The regulation of embryonic patterning and DNA replication by geminin. 2005, Pubmed
Rogers, Sox3 expression is maintained by FGF signaling and restricted to the neural plate by Vent proteins in the Xenopus embryo. 2007, Pubmed , Xenbase
Rogers, Xenopus Sox3 activates sox2 and geminin and indirectly represses Xvent2 expression to induce neural progenitor formation at the expense of non-neural ectodermal derivatives. 2008, Pubmed , Xenbase
Rozen, Primer3 on the WWW for general users and for biologist programmers. 1999, Pubmed
Sasai, Identifying the missing links: genes that connect neural induction and primary neurogenesis in vertebrate embryos. 1998, Pubmed
Seo, Geminin regulates neuronal differentiation by antagonizing Brg1 activity. 2005, Pubmed , Xenbase
Seo, Geminin's double life: chromatin connections that regulate transcription at the transition from proliferation to differentiation. 2006, Pubmed
Snape, Transcription factor AP-2 is tissue-specific in Xenopus and is closely related or identical to keratin transcription factor 1 (KTF-1). 1992, Pubmed , Xenbase
Spella, Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS in a specific phase of the cell cycle. 2007, Pubmed
Sullivan, foxD5a, a Xenopus winged helix gene, maintains an immature neural ectoderm via transcriptional repression that is dependent on the C-terminal domain. 2001, Pubmed , Xenbase
Sölter, Characterization of a subfamily of related winged helix genes, XFD-12/12'/12" (XFLIP), during Xenopus embryogenesis. 2000, Pubmed , Xenbase
Taylor, Tcf- and Vent-binding sites regulate neural-specific geminin expression in the gastrula embryo. 2006, Pubmed , Xenbase
Tuteja, SnapShot: forkhead transcription factors I. 2007, Pubmed
Uwanogho, Embryonic expression of the chicken Sox2, Sox3 and Sox11 genes suggests an interactive role in neuronal development. 1995, Pubmed
Wang, Sox3 expression identifies neural progenitors in persistent neonatal and adult mouse forebrain germinative zones. 2006, Pubmed
Wegner, From head to toes: the multiple facets of Sox proteins. 1999, Pubmed
Wegner, From stem cells to neurons and glia: a Soxist's view of neural development. 2005, Pubmed
Wijchers, In control of biology: of mice, men and Foxes. 2006, Pubmed
Yaklichkin, Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators. 2007, Pubmed
Yang, Beta-catenin/Tcf-regulated transcription prior to the midblastula transition. 2002, Pubmed , Xenbase
Zappone, Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. 2000, Pubmed
de Graaf, Hormone-inducible expression of secreted factors in zebrafish embryos. 1999, Pubmed
de la Calle-Mustienes, Xiro homeoproteins coordinate cell cycle exit and primary neuron formation by upregulating neuronal-fate repressors and downregulating the cell-cycle inhibitor XGadd45-gamma. 2002, Pubmed , Xenbase