Genomes and Genes
Gene Symbol: Rax
Description: retina and anterior neural fold homeobox
Alias: 7530406A22Rik, E130303K03Rik, ey-1, ey1, retinal homeobox protein Rx, Rx/rax homeoprotein, eyeless 1, retina and anterior neural fold homeobox protein
- Voronina V, Kozlov S, Mathers P, Lewandoski M. Conditional alleles for activation and inactivation of the mouse Rx homeobox gene. Genesis. 2005;41:160-4 pubmed....
- 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. ..
- Liu W, Lagutin O, Swindell E, Jamrich M, Oliver G. Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate. J Clin Invest. 2010;120:3568-77 pubmed publisher....
- Fujimura N, Taketo M, Mori M, Korinek V, Kozmik Z. Spatial and temporal regulation of Wnt/beta-catenin signaling is essential for development of the retinal pigment epithelium. Dev Biol. 2009;334:31-45 pubmed publisher..Combined, our data suggest that Wnt/beta-catenin signaling plays an essential role in development of RPE by maintaining or inducing expression of Mitf and Otx2. ..
- Tétreault N, Champagne M, Bernier G. The LIM homeobox transcription factor Lhx2 is required to specify the retina field and synergistically cooperates with Pax6 for Six6 trans-activation. Dev Biol. 2009;327:541-50 pubmed publisher..Our work reveals how two master regulators of eye development coordinate their action to sequentially promote tissue-specific transcriptional initiation and full activation of a retinal determinant gene. ..
- Wang Y, Dakubo G, Thurig S, Mazerolle C, Wallace V. Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development. 2005;132:5103-13 pubmed....
- Swindell E, Liu C, Shah R, Smith A, Lang R, Jamrich M. Eye formation in the absence of retina. Dev Biol. 2008;322:56-64 pubmed publisher..One involved in the formation of the eyeball and the second involved in the formation of the auxiliary eye structures. ..
- Lagutin O, Zhu C, Kobayashi D, Topczewski J, Shimamura K, Puelles L, et al. Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes Dev. 2003;17:368-79 pubmed..Furthermore, these results support the hypothesis that a Wnt signal gradient specifies posterior fates in the anterior neural plate. ..
- Furukawa T, Kozak C, Cepko C. rax, a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina. Proc Natl Acad Sci U S A. 1997;94:3088-93 pubmed..In this paper, we report the identification of a novel homeobox gene, rax (retina and anterior neural fold homeobox), whose expression pattern suggests an important role in eye development...
- Plageman T, Lang R. Generation of an Rx-tTA: TetOp-Cre knock-in mouse line for doxycycline regulated Cre activity in the Rx expression domain. PLoS ONE. 2012;7:e50426 pubmed publisher..This line has the potential to facilitate conditional knock-out experimentation to study early retina and/or posterior pituitary development. ..
- Mathers P, Grinberg A, Mahon K, Jamrich M. The Rx homeobox gene is essential for vertebrate eye development. Nature. 1997;387:603-7 pubmed..Mouse embryos carrying a null allele of this gene do not form optic cups and so do not develop eyes. The Rx gene family plays an important role in the establishment and/or proliferation of retinal progenitor cells. ..
- Hallonet M, Hollemann T, Pieler T, Gruss P. Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system. Genes Dev. 1999;13:3106-14 pubmed..On the basis of these results, we propose a model for a molecular cascade involved in the establishment of structures of the visual system. ..
- Swindell E, Bailey T, Loosli F, Liu C, Amaya Manzanares F, Mahon K, et al. Rx-Cre, a tool for inactivation of gene expression in the developing retina. Genesis. 2006;44:361-3 pubmed..Using these sequences, we made a Cre line that can be used for inactivation of gene expression in the developing retina. ..
- Tucker P, Laemle L, Munson A, Kanekar S, Oliver E, Brown N, et al. The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene. Genesis. 2001;31:43-53 pubmed..suggest that a small number of interacting genes are responsible, including at least one major recessive locus, ey1. Although predicted since the 1940s, these loci were never identified...
- Lu F, Kar D, Gruenig N, Zhang Z, Cousins N, Rodgers H, et al. Rax is a selector gene for mediobasal hypothalamic cell types. J Neurosci. 2013;33:259-72 pubmed publisher..Here, we demonstrate that the Retina and anterior neural fold homeobox (Rax) gene plays a key role in establishing ARC and VMH nuclei in mice...
- 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. ..
- 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..Collectively, these data indicate that BMP7 is required for retinal fissure formation and that its activity is needed, before SHH signalling, for the generation of PAX2-positive cells at the optic disc. ..
- 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..We demonstrate that the repression of Mitf by FGF is Chx10 dependent, indicating that FGF, Chx10 and Mitf are components of a pathway that determines and maintains the identity of the NR. ..
- Zhang L, Mathers P, Jamrich M. Function of Rx, but not Pax6, is essential for the formation of retinal progenitor cells in mice. Genesis. 2000;28:135-42 pubmed....
- Langer L, Taranova O, Sulik K, Pevny L. SOX2 hypomorphism disrupts development of the prechordal floor and optic cup. Mech Dev. 2012;129:1-12 pubmed publisher....
- Piché M, Robert S, Miceli D, Bronchti G. Environmental enrichment enhances auditory takeover of the occipital cortex in anophthalmic mice. Eur J Neurosci. 2004;20:3463-72 pubmed..This animal model will be useful for understanding neuronal mechanisms underlying some cross-modal sensory phenomena observed in blind or deaf humans. ..
- Aujla P, Naratadam G, Xu L, Raetzman L. Notch/Rbpjκ signaling regulates progenitor maintenance and differentiation of hypothalamic arcuate neurons. Development. 2013;140:3511-21 pubmed publisher..Taken together, our results demonstrate that Notch/Rbpjκ signaling regulates the generation and differentiation of Arc neurons, which contribute to homeostatic regulation of body size. ..
- Rohde K, Bering T, Furukawa T, Rath M. A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse. J Neurochem. 2017;143:100-111 pubmed publisherThe retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis...
- Qi Y, Zhang M, Li H, Frank J, Dai L, Liu H, et al. MicroRNA-29b regulates ethanol-induced neuronal apoptosis in the developing cerebellum through SP1/RAX/PKR cascade. J Biol Chem. 2014;289:10201-10 pubmed publisher..Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade...
- Laemle L, Ottenweller J. The relationship between circadian rhythmicity and vasoactive intestinal polypeptide in the suprachiasmatic nucleus of congenitally anophthalmic mice. Brain Res. 2001;917:105-11 pubmed..Our data provide the first definitive evidence that the presence of VIP neurons in the SCN is not sufficient for generation of circadian locomotor rhythms. ..
- Zhao S, Hung F, Colvin J, White A, Dai W, Lovicu F, et al. Patterning the optic neuroepithelium by FGF signaling and Ras activation. Development. 2001;128:5051-60 pubmed..In mouse embryos lacking FGF9, the retinal pigment epithelium extends into the presumptive neural retina, indicating a role of FGF9 in defining the boundary of the neural retina. ..
- 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. ..
- Wang Q, Chen S, Esumi N, Swain P, Haines H, Peng G, et al. QRX, a novel homeobox gene, modulates photoreceptor gene expression. Hum Mol Genet. 2004;13:1025-40 pubmed..Its homeodomain is nearly identical to that of Rx/Rax, a transcription factor that is essential for eye development, but it shares only limited homology elsewhere...
- Laemle L, Ottenweller J. Nonphotic entrainment of activity and temperature rhythms in anophthalmic mice. Physiol Behav. 1999;66:461-71 pubmed..Both sighted and anophthalmic mice were able to entrain to restricted wheel access, although not all animals responded. Mice that did not entrain showed either no effect of wheel locking or exhibited masking. ..
- Beck S. The anophthalmic mutant of the mouse. II. An association of anophthalmia and polydactyly. J Hered. 1963;54:79-83 pubmed
- Webster E, Silver A, Gonsalves N. The extracellular matrix between the optic vesicle and presumptive lens during lens morphogenesis in an anophthalmic strain of mice. Dev Biol. 1984;103:142-50 pubmed..B. Chase (1941, J. Morphol. 68, 279-301) that there may be abnormal contact between the optic vesicle and presumptive lens ectoderm in the mutant strain, although there is a differing view on the cause of the abnormal contact. ..
- Olavarria J, Van Sluyters R. Callosal connections of the posterior neocortex in normal-eyed, congenitally anophthalmic, and neonatally enucleated mice. J Comp Neurol. 1984;230:249-68 pubmed..Finally, examination of coronal sections indicates that the laminar distribution of callosal connections develops normally in both groups of eyeless mice. ..
- Li H, Wagner E, McCaffery P, Smith D, Andreadis A, Drager U. A retinoic acid synthesizing enzyme in ventral retina and telencephalon of the embryonic mouse. Mech Dev. 2000;95:283-9 pubmed..From here it extends via the piriform cortex into the lower part of the septum. Of the three RALDHs, RALDH3 shows the strongest predilection for epithelia. ..
- 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..The results suggest that careful manipulation of the Pax6 regulatory circuit may facilitate the generation of retinal and pigment epithelium cells from embryonic or induced pluripotent stem cells. ..
- Laemle L, Ottenweller J, Fugaro C. Diurnal variations in vasoactive intestinal polypeptide-like immunoreactivity in the suprachiasmatic nucleus of congenitally anophthalmic mice. Brain Res. 1995;688:203-8 pubmed..These observations support the hypothesis that expression of VIP is related to regulation of circadian rhythms by the SCN. ..
- Kaiserman Abramof I, Graybiel A, Nauta W. The thalamic projection to cortical area 17 in a congenitally anophthalmic mouse strain. Neuroscience. 1980;5:41-52 pubmed
- Chase H. Studies on an Anophthalmic Strain of Mice. IV. a Second Major Gene for Anophthalmia. Genetics. 1944;29:264-9 pubmed
- Schwarz M, Cecconi F, Bernier G, Andrejewski N, Kammandel B, Wagner M, et al. Spatial specification of mammalian eye territories by reciprocal transcriptional repression of Pax2 and Pax6. Development. 2000;127:4325-34 pubmed..Based on our findings, we propose a model for Pax gene regulation that establishes the proper spatial regionalization of the mammalian visual system. ..
- Wagner E, McCaffery P, Drager U. Retinoic acid in the formation of the dorsoventral retina and its central projections. Dev Biol. 2000;222:460-70 pubmed..These observations indicate that the dorsoventral axis of the embryonic eye anlage determines the functional coordinates of both vision and eye movements in the adult. ..
- Cunningham D, Xiao Q, Chatterjee A, Sulik K, Juriloff D, Elder F, et al. exma: an X-linked insertional mutation that disrupts forebrain and eye development. Mamm Genome. 2002;13:179-85 pubmed..From the physical mapping results, we propose a model of the gross rearrangements that accompanied transgene integration and discuss its implications for evaluating candidate genes for exma. ..
- Brinkmeier M, Davis S, Carninci P, MacDonald J, Kawai J, Ghosh D, et al. Discovery of transcriptional regulators and signaling pathways in the developing pituitary gland by bioinformatic and genomic approaches. Genomics. 2009;93:449-60 pubmed publisher..These genes are exciting candidates for regulators of pituitary development and function. ..
- Muranishi Y, Terada K, Inoue T, Katoh K, Tsujii T, Sanuki R, et al. An essential role for RAX homeoprotein and NOTCH-HES signaling in Otx2 expression in embryonic retinal photoreceptor cell fate determination. J Neurosci. 2011;31:16792-807 pubmed publisher..We found that the RAX homeoprotein interacts with EELPOT to transactivate Otx2, mainly in the final cell cycle of retinal progenitors...
- Hatakeyama J, Bessho Y, Katoh K, Ookawara S, Fujioka M, Guillemot F, et al. Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation. Development. 2004;131:5539-50 pubmed....
- Laemle L, Rusa R. VIP-like immunoreactivity in the suprachiasmatic nuclei of a mutant anophthalmic mouse. Brain Res. 1992;589:124-8 pubmed..Within the SCN, the distribution of VIP-immunoreactive cells was more diffuse in anophthalmic mice than in the controls; immunoreactive neurons were frequently observed in ectopic locations in the mutant animals. ..
- Zwaan J, Silver J. Crystallin synthesis in the lens rudiment of a strain of mice with congenital anophthalmia. Exp Eye Res. 1983;36:551-7 pubmed..This indicates that the optic vesicle in this mutant is capable of inducing a lens, while the surface ectoderm can respond to the stimulus in a normal fashion. ..
- 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. ..
- Laemle L, Puszkarczuk M, Feinberg R. Apoptosis in early ocular morphogenesis in the mouse. Brain Res Dev Brain Res. 1999;112:129-33 pubmed..Our data indicate that apoptosis plays a role in normal ocular morphogenesis and provides the groundwork for studies of abnormal ocular development. ..
- Mikkola I, Bruun J, Holm T, Johansen T. Superactivation of Pax6-mediated transactivation from paired domain-binding sites by dna-independent recruitment of different homeodomain proteins. J Biol Chem. 2001;276:4109-18 pubmed..The paired-like homeodomain protein Rax behaved similarly to Pax6DeltaPD...
- Beck S. The anophthalmic mutant of the mouse. I. Genetic contribution to the anophthalmic phenotype. J Hered. 1963;54:39-44 pubmed
- de Melo J, Zibetti C, Clark B, Hwang W, Miranda Angulo A, Qian J, et al. Lhx2 Is an Essential Factor for Retinal Gliogenesis and Notch Signaling. J Neurosci. 2016;36:2391-405 pubmed publisher..pathway genes including Notch1, Dll1, and Dll3 and gliogenic transcription factors such as Hes1, Hes5, Sox8, and Rax. Conditional knock-out of Lhx2 resulted in a rapid downregulation of Notch pathway genes and loss of Notch ..
- Laemle L, Hori N, Strominger N, Tan Y, Carpenter D. Physiological and anatomical properties of the suprachiasmatic nucleus of an anophthalmic mouse. Brain Res. 2002;953:73-81 pubmed..These data suggest that the characteristic irregular firing pattern of anophthalmics, and of controls at night, results from extrinsic, at least in part, GABAergic input. ..
- Bennett R, Blalock W, Choi E, Lee Y, Zhang Y, Zhou L, et al. RAX is required for fly neuronal development and mouse embryogenesis. Mech Dev. 2008;125:777-85 pubmed publisherb>RAX was originally discovered as the unique cellular activator for the dsRNA-dependent, interferon-inducible protein kinase PKR...
- Bernier G, Vukovich W, Neidhardt L, Herrmann B, Gruss P. Isolation and characterization of a downstream target of Pax6 in the mammalian retinal primordium. Development. 2001;128:3987-94 pubmed..Taken together, our results provide evidence that Necab is genetically downstream of Pax6 and that it is a part of a signal transduction pathway in retina development. ..
- Rhoades R, Mooney R, Fish S. A comparison of visual callosal organization in normal, bilaterally enucleated and congenitally anophthalmic mice. Exp Brain Res. 1984;56:92-105 pubmed..One of these was always located at the 17-18a border, and here the laminar distribution of labelled cells and anterograde labelling was the same as in the normals.(ABSTRACT TRUNCATED AT 400 WORDS) ..
- Beck S. FREQUENCIES OF TERATOLOGIES AMONG HOMOZYGOUS NORMAL MICE COMPARED WITH THOSE HETEROZYGOUS FOR ANOPHTHALMIA. Nature. 1963;200:810-1 pubmed
- BARBER A. The effects of maternal hypoxia on inheritance of recessive blindness in mice. Am J Ophthalmol. 1957;44:94-102 pubmed
- Faradji Prevautel H, Cespuglio R, Jouvet M. Circadian rest-activity rhythms in the anophthalmic, monocular and binocular ZRDCT/An mice. Retinal and serotoninergic (raphe) influences. Brain Res. 1990;526:207-16 pubmed..Further, a circadian variation of this signal is superimposed to that of the waking state amount. Such circadian variations are synchronized to the L/D cycle in C57 Black/6 animals and free running in the AN mice...
- Yamada R, Mizutani Koseki Y, Hasegawa T, Osumi N, Koseki H, Takahashi N. Cell-autonomous involvement of Mab21l1 is essential for lens placode development. Development. 2003;130:1759-70 pubmed..We conclude that Mab21l1 expression dependent on PAX6 is essential for lens placode growth and for formation of the lens vesicle; lack of Mab21l1 expression causes reduced expression of Foxe3 in a cell-autonomous manner. ..
- Wataya T, Ando S, Muguruma K, Ikeda H, Watanabe K, Eiraku M, et al. Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation. Proc Natl Acad Sci U S A. 2008;105:11796-801 pubmed publisher..factors during early differentiation steps induces efficient generation of rostral hypothalamic-like progenitors (Rax(+)/Six3(+)/Vax1(+)) in mouse ES cell-derived neuroectodermal cells...
- Cullen M, Kaiserman Abramof I. Cytological organization of the dorsal lateral geniculate nuclei in mutant anophthalmic and postnatally enucleated mice. J Neurocytol. 1976;5:407-24 pubmed..The possibility that some of these large replacement terminals originate from cortical or recurrent collateral axons is considered. ..
- Sakakura E, Eiraku M, Takata N. Specification of embryonic stem cell-derived tissues into eye fields by Wnt signaling using rostral diencephalic tissue-inducing culture. Mech Dev. 2016;141:90-9 pubmed publisher..Taking advantage of embryonic stem cell (ESC) culture using a Rax reporter line to monitor rostral diencephalon formation, we found that ESC-derived tissues at day 7 grown in ..
- Chabot N, Charbonneau V, Laramée M, Tremblay R, Boire D, Bronchti G. Subcortical auditory input to the primary visual cortex in anophthalmic mice. Neurosci Lett. 2008;433:129-34 pubmed publisher..In particular, we find no evidence of a direct projection from the auditory mesencephalon to the cortex in this animal model of blindness. ..