Genomes and Genes
Gene Symbol: Vsx2
Description: visual system homeobox 2
Alias: Chx10, Hox-10, Hox10, visual system homeobox 2, C. elegans ceh-10 homeo domain containing homolog, ceh-10 homeodomain-containing homolog, homeobox protein CHX10, ocular retardation
- Mu X, Fu X, Beremand P, Thomas T, Klein W. Gene regulation logic in retinal ganglion cell development: Isl1 defines a critical branch distinct from but overlapping with Pou4f2. Proc Natl Acad Sci U S A. 2008;105:6942-7 pubmed publisher..They also reveal that identical RGC expression patterns are achieved by different combinations of divergent inputs from upstream transcription factors. ..
- Iulianella A, Sharma M, Durnin M, Vanden Heuvel G, Trainor P. Cux2 (Cutl2) integrates neural progenitor development with cell-cycle progression during spinal cord neurogenesis. Development. 2008;135:729-41 pubmed publisher..Thus our work defines novel roles for Cux2 as a transcription factor that integrates cell-cycle progression with neural progenitor development during spinal cord neurogenesis. ..
- Bone Larson C, Basu S, Radel J, Liang M, Perozek T, Kapousta Bruneau N, et al. Partial rescue of the ocular retardation phenotype by genetic modifiers. J Neurobiol. 2000;42:232-47 pubmedThe or(J) allele of the murine ocular retardation mutation is caused by a premature stop codon in the homeodomain of the Chx10 gene...
- Reichman S, Kalathur R, Lambard S, Aït Ali N, Yang Y, Lardenois A, et al. The homeobox gene CHX10/VSX2 regulates RdCVF promoter activity in the inner retina. Hum Mol Genet. 2010;19:250-61 pubmed publisher..transcription factors, chosen based upon their expression pattern, we identified the homeodomain proteins CHX10/VSX2, VSX1 and PAX4, as well as the zinc finger protein SP3, as factors that can stimulate both the mouse and ..
- Fu X, Sun H, Klein W, Mu X. Beta-catenin is essential for lamination but not neurogenesis in mouse retinal development. Dev Biol. 2006;299:424-37 pubmed..The results further imply that retinal lamination and retinal cell differentiation are genetically separable processes. ..
- Lu Q, Sun T, Zhu Z, Ma N, Garcia M, Stiles C, et al. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell. 2002;109:75-86 pubmed..Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons. ..
- Clark A, Yun S, Veien E, Wu Y, Chow R, Dorsky R, et al. Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Brain Res. 2008;1192:99-113 pubmedb>Chx10/Vsx2 and Vsx1 are the only Paired-like CVC (Prd-L:CVC) homeobox genes in the mouse genome. Both are expressed in the retina and have important but distinct roles in retinal development...
- Bharti K, Liu W, Csermely T, Bertuzzi S, Arnheiter H. Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF. Development. 2008;135:1169-78 pubmed publisher..Moreover, in mutants of the retinal Mitf regulator Chx10 (Vsx2), reduced cell proliferation and abnormal pigmentation of the retina are associated with a preferential ..
- Li S, Mo Z, Yang X, Price S, Shen M, Xiang M. Foxn4 controls the genesis of amacrine and horizontal cells by retinal progenitors. Neuron. 2004;43:795-807 pubmed..Our data suggest a model in which Foxn4 cooperates with other key retinogenic factors to mediate the multipotent differentiation of retinal progenitors. ..
- Matsushima D, Heavner W, Pevny L. Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6. Development. 2011;138:443-54 pubmed publisher..Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina. ..
- Bharti K, Gasper M, Ou J, Brucato M, Clore Gronenborn K, Pickel J, et al. A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development. PLoS Genet. 2012;8:e1002757 pubmed publisher..by inhibiting canonical WNT signaling and stimulating the expression of retinogenic genes, including Six6 and Vsx2. Our results demonstrate that in conjunction with Mitf/Tfec Pax6 acts as an anti-retinogenic factor, whereas in ..
- Peng C, Yajima H, Burns C, Zon L, Sisodia S, Pfaff S, et al. Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord. Neuron. 2007;53:813-27 pubmed..Thus, our study provides insight into the cell-extrinsic signaling that controls combinatorial transcription factor profiles involved in regulating the process of interneuron subtype diversification. ..
- Rowan S, Cepko C. Genetic analysis of the homeodomain transcription factor Chx10 in the retina using a novel multifunctional BAC transgenic mouse reporter. Dev Biol. 2004;271:388-402 pubmedb>Chx10 is a homeobox-containing transcription factor critical for progenitor cell proliferation and bipolar cell determination in the developing retina...
- Dhomen N, Balaggan K, Pearson R, Bainbridge J, Levine E, Ali R, et al. Absence of chx10 causes neural progenitors to persist in the adult retina. Invest Ophthalmol Vis Sci. 2006;47:386-96 pubmed..This study used Chx10-/- (ocular retardation) mice to investigate how lack of Chx10 affects progenitor/stem cell behavior in the retina and ciliary ..
- Ding Q, Chen H, Xie X, Libby R, Tian N, Gan L. BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons. J Neurosci. 2009;29:3992-4003 pubmed publisher..Thus, BARHL2 appears to have numerous roles in retinal development, including regulating neuronal subtype specification, differentiation, and survival. ..
- Cai Z, Feng G, Zhang X. Temporal requirement of the protein tyrosine phosphatase Shp2 in establishing the neuronal fate in early retinal development. J Neurosci. 2010;30:4110-9 pubmed publisher..Together, these results demonstrate that Shp2 mediates FGF-Ras signaling to control retinal progenitor cell fate. ..
- Joshi K, Lee S, Lee B, Lee J, Lee S. LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons. Neuron. 2009;61:839-51 pubmed publisher..Thus, LMO4 plays essential roles in directing a balanced generation of inhibitory and excitatory neurons in the ventral spinal cord. ..
- Tang K, Xie X, Park J, Jamrich M, Tsai S, Tsai M. COUP-TFs regulate eye development by controlling factors essential for optic vesicle morphogenesis. Development. 2010;137:725-34 pubmed publisher..Taken together, our findings reveal novel and distinct cell-intrinsic mechanisms mediated by COUP-TF genes to direct the specification and differentiation of progenitor cells, and that COUP-TFs are crucial for dorsalization of the eye. ..
- Ma C, Papermaster D, Cepko C. A unique pattern of photoreceptor degeneration in cyclin D1 mutant mice. Proc Natl Acad Sci U S A. 1998;95:9938-43 pubmed..We also tested whether expression of a bcl-2 transgene could prevent the death and found that it could not. ..
- Poche R, Kwan K, Raven M, Furuta Y, Reese B, Behringer R. Lim1 is essential for the correct laminar positioning of retinal horizontal cells. J Neurosci. 2007;27:14099-107 pubmed..This study is the first to describe a cell type-specific genetic program that is essential for targeting a discrete retinal neuron population to the proper lamina. ..
- Burmeister M, Novak J, Liang M, Basu S, Ploder L, Hawes N, et al. Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat Genet. 1996;12:376-84 pubmedb>Ocular retardation (or) is a murine eye mutation causing microphthalmia, a thin hypocellular retina and optic nerve aplasia...
- Burrill J, Moran L, Goulding M, Saueressig H. PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development. Development. 1997;124:4493-503 pubmed..These results demonstrate that the early activity of patterning genes in the ventricular zone determines interneuron identity in the spinal cord. ..
- Martins R, Zindy F, Donovan S, Zhang J, Pounds S, Wey A, et al. N-myc coordinates retinal growth with eye size during mouse development. Genes Dev. 2008;22:179-93 pubmed publisher..We propose that N-myc lies upstream of the cell cycle machinery in the developing mouse retina and thus coordinates the growth of both the retina and eye through extrinsic cues. ..
- Horsford D, Nguyen M, Sellar G, Kothary R, Arnheiter H, McInnes R. Chx10 repression of Mitf is required for the maintenance of mammalian neuroretinal identity. Development. 2005;132:177-87 pubmed..the cells of the optic vesicle (OV) become either neuroretinal progenitors expressing the transcription factor Chx10, or retinal pigment epithelium (RPE) progenitors expressing the transcription factor Mitf...
- Nguyen M, Arnheiter H. Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF. Development. 2000;127:3581-91 pubmed..results in the maintenance of MITF in the distal optic epithelium, lack of expression of the neuroretinal-specific CHX10 transcription factor, and conversion of this epithelium into a pigmented monolayer...
- Wong G, Conger S, Burmeister M. Mapping of genetic modifiers affecting the eye phenotype of ocular retardation (Chx10or-J) mice. Mamm Genome. 2006;17:518-25 pubmedb>Ocular retardation is a recessive murine mutation whose phenotypic expression is greatly affected by genetic background effects...
- Rainger J, Keighren M, Keene D, Charbonneau N, Rainger J, Fisher M, et al. A trans-acting protein effect causes severe eye malformation in the Mp mouse. PLoS Genet. 2013;9:e1003998 pubmed publisher..The prediction of similar trans-acting protein effects will be an important challenge in the medical interpretation of human mutations from whole exome sequencing. ..
- Le T, Wroblewski E, Patel S, Riesenberg A, Brown N. Math5 is required for both early retinal neuron differentiation and cell cycle progression. Dev Biol. 2006;295:764-78 pubmed..Thus, Math5 orchestrates neurogenesis in multiple ways, regulating both intrinsic and extrinsic processes. ..
- Lee H, Wroblewski E, Philips G, Stair C, Conley K, Reedy M, et al. Multiple requirements for Hes 1 during early eye formation. Dev Biol. 2005;284:464-78 pubmed..Together, these studies demonstrate that Hes1, like Pax6, simultaneously regulates multiple developmental processes during optic development. ..
- Dorval K, Bobechko B, Fujieda H, Chen S, Zack D, Bremner R. CHX10 targets a subset of photoreceptor genes. J Biol Chem. 2006;281:744-51 pubmedThe homeobox gene CHX10 is required for retinal progenitor cell proliferation early in retinogenesis and subsequently for bipolar neuron differentiation...
- Pierani A, Moran Rivard L, Sunshine M, Littman D, Goulding M, Jessell T. Control of interneuron fate in the developing spinal cord by the progenitor homeodomain protein Dbx1. Neuron. 2001;29:367-84 pubmed..Thus, a single progenitor homeodomain transcription factor coordinates many of the differentiated properties of one class of interneurons generated in the ventral spinal cord. ..
- Green E, Stubbs J, Levine E. Genetic rescue of cell number in a mouse model of microphthalmia: interactions between Chx10 and G1-phase cell cycle regulators. Development. 2003;130:539-52 pubmedInsufficient cell number is a primary cause of failed retinal development in the Chx10 mutant mouse. To determine if Chx10 regulates cell number by antagonizing p27(Kip1) activity, we generated Chx10, p27(Kip1) double null mice...
- Medina C, Mazerolle C, Wang Y, Berube N, Coupland S, Gibbons R, et al. Altered visual function and interneuron survival in Atrx knockout mice: inference for the human syndrome. Hum Mol Genet. 2009;18:966-77 pubmed publisher..These results implicate a role for Atrx in interneuron survival and differentiation...
- Elshatory Y, Deng M, Xie X, Gan L. Expression of the LIM-homeodomain protein Isl1 in the developing and mature mouse retina. J Comp Neurol. 2007;503:182-97 pubmed..As bipolar cell development proceeds from P5-10 the colocalization of Isl1 and the pan-bipolar cell marker Chx10 reveals the organization of ON-center bipolar cell nuclei to the upper portion of the inner nuclear layer...
- de Melo J, Qiu X, Du G, Cristante L, Eisenstat D. Dlx1, Dlx2, Pax6, Brn3b, and Chx10 homeobox gene expression defines the retinal ganglion and inner nuclear layers of the developing and adult mouse retina. J Comp Neurol. 2003;461:187-204 pubmed..1999] J. Comp. Neurol. 217-237). At E13.5, the expression of four homeodomain proteins, DLX2, BRN3b, PAX6, and CHX10, define distinct yet overlapping domains in the retinal neuroepithelium...
- Rowan S, Cepko C. A POU factor binding site upstream of the Chx10 homeobox gene is required for Chx10 expression in subsets of retinal progenitor cells and bipolar cells. Dev Biol. 2005;281:240-55 pubmed..An analysis of the regulatory region of the retinal homeodomain transcription factor, Chx10, was carried out using in ovo electroporations in chick and transgenic mice...
- Arber S, Han B, Mendelsohn M, Smith M, Jessell T, Sockanathan S. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron. 1999;23:659-74 pubmed..These findings show that HB9 has an essential function in consolidating the identity of postmitotic MNs. ..
- Morcillo J, Martinez Morales J, Trousse F, Fermin Y, Sowden J, Bovolenta P. Proper patterning of the optic fissure requires the sequential activity of BMP7 and SHH. Development. 2006;133:3179-90 pubmed..Furthermore, SHH addition re-establishes Pax2 expression in late optic cups derived from ocular retardation (or) embryos, where optic disc development is impaired owing to the near absence of SHH-producing RGC...
- Wellik D, Capecchi M. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science. 2003;301:363-7 pubmedMice in which all members of the Hox10 or Hox11 paralogous group are disrupted provide evidence that these Hox genes are involved in global patterning of the axial and appendicular skeleton...
- Feng L, Xie X, Joshi P, Yang Z, Shibasaki K, Chow R, et al. Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina. Development. 2006;133:4815-25 pubmed..Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes. ..
- Matise M, Epstein D, Park H, Platt K, Joyner A. Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system. Development. 1998;125:2759-70 pubmed
- Liu B, Liu Z, Chen T, Li H, Qiang B, Yuan J, et al. Selective expression of Bhlhb5 in subsets of early-born interneurons and late-born association neurons in the spinal cord. Dev Dyn. 2007;236:829-35 pubmed..At late stages of development, Bhlhb5 expression is detected in a subset of late-born dorsal association interneurons that migrate into the uppermost layer of the dorsal horn. ..
- Raviv S, Bharti K, Rencus Lazar S, Cohen Tayar Y, Schyr R, Evantal N, et al. PAX6 regulates melanogenesis in the retinal pigmented epithelium through feed-forward regulatory interactions with MITF. PLoS Genet. 2014;10:e1004360 pubmed publisher..This study exemplifies how one kernel gene pivotal in organ formation accomplishes a lineage-specific role during terminal differentiation of a single lineage. ..
- Morikawa Y, Hisaoka T, Senba E. Characterization of Foxp2-expressing cells in the developing spinal cord. Neuroscience. 2009;162:1150-62 pubmed publisher..with some homeodomain transcription factors revealed that Foxp2-expressing neurons were Pax2(+), En1(+), Evx1(-), Chx10(-), Gata3(-), and Lhx3(-) V1 interneurons in the intermediate zone throughout the ventral spinal cord, indicating ..
- Holz A, Kollmus H, Ryge J, Niederkofler V, Dias J, Ericson J, et al. The transcription factors Nkx2.2 and Nkx2.9 play a novel role in floor plate development and commissural axon guidance. Development. 2010;137:4249-60 pubmed publisher..As both factors affect floor plate development, control of commissural axon trajectories might be the underlying mechanism. ..
- Fotaki V, Smith R, Pratt T, Price D. Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/?-catenin signalling in the developing nasal retina of the mouse. Dev Biol. 2013;380:299-313 pubmed publisher..Our results reveal a new role of Foxg1 in limiting CM development in the nasal peripheral retina and add a new molecular player in the developmental network involved in CM specification. ..
- Baumer N, Marquardt T, Stoykova A, Spieler D, Treichel D, Ashery Padan R, et al. Retinal pigmented epithelium determination requires the redundant activities of Pax2 and Pax6. Development. 2003;130:2903-15 pubmed..Together, these results demonstrate that the redundant activities of Pax2 and Pax6 direct the determination of RPE, potentially by directly controlling the expression of RPE determinants. ..
- Bai C, Stephen D, Joyner A. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev Cell. 2004;6:103-15 pubmed..Therefore, in the spinal cord all Hh signaling is Gli dependent. Furthermore, a combination of Gli2 and Gli3 is required to regulate motor neuron development and spatial patterning of ventral spinal cord progenitors. ..
- Liu I, Chen J, Ploder L, Vidgen D, van der Kooy D, Kalnins V, et al. Developmental expression of a novel murine homeobox gene (Chx10): evidence for roles in determination of the neuroretina and inner nuclear layer. Neuron. 1994;13:377-93 pubmed..We describe a 39 kDa murine polypeptide (Chx10) with a homeodomain 82% identical to that of the nematode protein ceh-10...
- Nishida A, Furukawa A, Koike C, Tano Y, Aizawa S, Matsuo I, et al. Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat Neurosci. 2003;6:1255-63 pubmed..Thus, Otx2 is a key regulatory gene for the cell fate determination of retinal photoreceptor cells. Our results reveal the key molecular steps required for photoreceptor cell-fate determination and pinealocyte development. ..
- Donovan S, Schweers B, Martins R, Johnson D, Dyer M. Compensation by tumor suppressor genes during retinal development in mice and humans. BMC Biol. 2006;4:14 pubmed..Together, these data suggest a model that explains why humans are susceptible to retinoblastoma following RB1 loss, but mice require both Rb and p107 gene inactivation. ..
- Cunningham J, Levine E, Zindy F, Goloubeva O, Roussel M, Smeyne R. The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively to control cell cycle exit. Mol Cell Neurosci. 2002;19:359-74 pubmed..These data indicate that select retinal cells express both p19(Ink4d) and p27(Kip1) and that they act cooperatively to ensure cell cycle exit. ..
- Scardigli R, Schuurmans C, Gradwohl G, Guillemot F. Crossregulation between Neurogenin2 and pathways specifying neuronal identity in the spinal cord. Neuron. 2001;31:203-17 pubmed..Thus, neuronal differentiation involves crossregulatory interactions between a bHLH-driven program of neurogenesis and genetic pathways specifying progenitor and neuronal identity in the spinal cord. ..
- Ma L, Cantrup R, Varrault A, Colak D, Klenin N, Gotz M, et al. Zac1 functions through TGFbetaII to negatively regulate cell number in the developing retina. Neural Dev. 2007;2:11 pubmed..This raises the intriguing possibility that tumorigenicity may also be associated with the loss of feedback inhibition in mature tissues. ..
- Mu X, Fu X, Sun H, Liang S, Maeda H, Frishman L, et al. Ganglion cells are required for normal progenitor- cell proliferation but not cell-fate determination or patterning in the developing mouse retina. Curr Biol. 2005;15:525-30 pubmed..Intrinsic rather than extrinsic factors are likely to play the critical roles in determining retinal cell fate. ..
- Spencer C, Pajovic S, Devlin H, Dinh Q, Corson T, Gallie B. Distinct patterns of expression of the RB gene family in mouse and human retina. Gene Expr Patterns. 2005;5:687-94 pubmed..The RB gene family is dynamically and variably expressed through retinal development in specific retinal cells. ..
- Smith A, Miller L, Radice G, Ashery Padan R, Lang R. Stage-dependent modes of Pax6-Sox2 epistasis regulate lens development and eye morphogenesis. Development. 2009;136:2977-85 pubmed publisher..These data support a model in which the mode of Pax6-Sox2 inter-regulation is stage-dependent and suggest an underlying mechanism in which DNA binding site availability is regulated. ..
- Manuel M, Pratt T, Liu M, Jeffery G, Price D. Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance. BMC Dev Biol. 2008;8:59 pubmed publisher..Here, we examined the consequences of over-expression for the eye and its axonal connections...
- Ericson J, Rashbass P, Schedl A, Brenner Morton S, Kawakami A, van Heyningen V, et al. Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell. 1997;90:169-80 pubmed..2. Pax6 establishes distinct ventral progenitor cell populations and controls the identity of motor neurons and ventral interneurons, mediating graded Shh signaling in the ventral spinal cord and hindbrain. ..
- Burns C, Zhang J, Brown E, Van Bibber A, van Es J, Clevers H, et al. Investigation of Frizzled-5 during embryonic neural development in mouse. Dev Dyn. 2008;237:1614-26 pubmed publisher..Thus, the function of Fzd5 during eye development appears to be species-dependent. ..