Gene Symbol: Pou4f2
Description: POU domain, class 4, transcription factor 2
Alias: Brn-3.2, Brn-3b, Brn3b, Pou4f-rs1, mBrn3-3R, POU domain, class 4, transcription factor 2, POU domain, class 4, transcription factor, related sequence 1, brain-3B, brain-specific homeobox/POU domain protein 3B
Species: mouse
Products:     Pou4f2

Top Publications

  1. 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. ..
  2. Erkman L, Yates P, McLaughlin T, McEvilly R, Whisenhunt T, O Connell S, et al. A POU domain transcription factor-dependent program regulates axon pathfinding in the vertebrate visual system. Neuron. 2000;28:779-92 pubmed
    ..elegans homolog, UNC-115. Our findings provide insights into a Brn-3.2-directed hierarchical program linking signaling events to cytoskeletal changes required for axon pathfinding. ..
  3. Brzezinski J, Prasov L, Glaser T. Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle. Dev Biol. 2012;365:395-413 pubmed publisher
    ..These data are consistent with progressive and temporal restriction models for retinal neurogenesis, in which environmental factors influence the final histotypic choice. ..
  4. Fu X, Kiyama T, Li R, Russell M, Klein W, Mu X. Epitope-tagging Math5 and Pou4f2: new tools to study retinal ganglion cell development in the mouse. Dev Dyn. 2009;238:2309-17 pubmed publisher
    ..Here, we overcome these limitations by constructing genetically engineered alleles for Math5 and Pou4f2, two genes required for retinal ganglion cell (RGC) development...
  5. Budhram Mahadeo V, Parker M, Latchman D. POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element. Mol Cell Biol. 1998;18:1029-41 pubmed
    ..These observations and their implications for transcriptional regulation by the ER are discussed. ..
  6. 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. ..
  7. Das G, Choi Y, Sicinski P, Levine E. Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells. Neural Dev. 2009;4:15 pubmed publisher
  8. Feng L, Xie Z, Ding Q, Xie X, Libby R, Gan L. MATH5 controls the acquisition of multiple retinal cell fates. Mol Brain. 2010;3:36 pubmed publisher
    ..Collectively, these data suggest that Math5 regulates the generation of multiple retinal cell types via different mechanisms during retinogenesis. ..
  9. 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

More Information


  1. Gan L, Wang S, Huang Z, Klein W. POU domain factor Brn-3b is essential for retinal ganglion cell differentiation and survival but not for initial cell fate specification. Dev Biol. 1999;210:469-80 pubmed
    ..These results suggest that Brn-3b regulates the activity of genes whose products play essential roles in the formation of retinal ganglion cell axons. ..
  2. Jain V, Ravindran E, Dhingra N. Differential expression of Brn3 transcription factors in intrinsically photosensitive retinal ganglion cells in mouse. J Comp Neurol. 2012;520:742-55 pubmed publisher
    ..The Brn3 family of class IV POU-domain transcription factors (Brn3a, Brn3b, and Brn3c) is involved in the regulation of differentiation, dendritic stratification, and axonal projection of ..
  3. Causeret F, Danne F, Ezan F, Sotelo C, Bloch Gallego E. Slit antagonizes netrin-1 attractive effects during the migration of inferior olivary neurons. Dev Biol. 2002;246:429-40 pubmed
    ..Our results indicate that slit silences the attractive effects of netrin-1 and could participate in the correct ventral positioning of ION, stopping the migration when cell bodies reach the floor-plate. ..
  4. Turner E, Jenne K, Rosenfeld M. Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid. Neuron. 1994;12:205-18 pubmed
    ..Our analysis suggests that in the CNS Brn-3.2 is selectively expressed in postmitotic neurons, implying a role in specifying terminally differentiated neuronal phenotypes. ..
  5. Badea T, Nathans J. Morphologies of mouse retinal ganglion cells expressing transcription factors Brn3a, Brn3b, and Brn3c: analysis of wild type and mutant cells using genetically-directed sparse labeling. Vision Res. 2011;51:269-79 pubmed publisher
    ..Previous work has shown that the transcription factor Brn3b/Pou4f2 plays a major role in the development and survival of many RGCs...
  6. Xiang M, Gan L, Li D, Zhou L, Chen Z, Wagner D, et al. Role of the Brn-3 family of POU-domain genes in the development of the auditory/vestibular, somatosensory, and visual systems. Cold Spring Harb Symp Quant Biol. 1997;62:325-36 pubmed
  7. Xiang M. Requirement for Brn-3b in early differentiation of postmitotic retinal ganglion cell precursors. Dev Biol. 1998;197:155-69 pubmed
  8. Jin K, Jiang H, Mo Z, Xiang M. Early B-cell factors are required for specifying multiple retinal cell types and subtypes from postmitotic precursors. J Neurosci. 2010;30:11902-16 pubmed publisher
    ..horizontal cells, and that their expression in ganglion cells depends on the ganglion cell specification factor Brn3b. Misexpressed Ebfs bias retinal precursors toward the fates of non-AII glycinergic amacrine, type 2 OFF-cone ..
  9. Trieu M, Rhee J, Fedtsova N, Turner E. Autoregulatory sequences are revealed by complex stability screening of the mouse brn-3.0 locus. J Neurosci. 1999;19:6549-58 pubmed
    ..This region also mediates transactivation by the closely related protein Brn-3.2, suggesting a regulatory cascade of POU proteins in specific neurons in which Brn-3.2 expression precedes Brn-3.0. ..
  10. Cho J, Mu X, Wang S, Klein W. Retinal ganglion cell death and optic nerve degeneration by genetic ablation in adult mice. Exp Eye Res. 2009;88:542-52 pubmed publisher
    ..To achieve this, we took advantage of Pou4f2 (Brn3b), a gene activated immediately as RGCs begin to differentiate and expressed throughout life...
  11. Mao C, Kiyama T, Pan P, Furuta Y, Hadjantonakis A, Klein W. Eomesodermin, a target gene of Pou4f2, is required for retinal ganglion cell and optic nerve development in the mouse. Development. 2008;135:271-80 pubmed
    ..This has revealed the existence of a Pou domain transcription factor, Pou4f2, that occupies a key node in the RGC gene regulatory network and that is essential for RGC differentiation...
  12. Taranova O, Magness S, Fagan B, Wu Y, Surzenko N, Hutton S, et al. SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev. 2006;20:1187-202 pubmed
  13. He X, Treacy M, Simmons D, Ingraham H, Swanson L, Rosenfeld M. Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature. 1989;340:35-41 pubmed
  14. Erkman L, McEvilly R, Luo L, Ryan A, Hooshmand F, O Connell S, et al. Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development. Nature. 1996;381:603-6 pubmed
    ..Mutation of Brn-3.1 results in complete deafness, owing to a failure of hair cells to appear in the inner ear, with subsequent loss of cochlear and vestibular ganglia. ..
  15. 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. ..
  16. 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...
  17. Moshiri A, Gonzalez E, Tagawa K, Maeda H, Wang M, Frishman L, et al. Near complete loss of retinal ganglion cells in the math5/brn3b double knockout elicits severe reductions of other cell types during retinal development. Dev Biol. 2008;316:214-27 pubmed publisher
    ..In this study, we observed that Math5 and Brn3b double null mice exhibited over a 99% reduction in the number of RGCs during development...
  18. 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. ..
  19. McEvilly R, Erkman L, Luo L, Sawchenko P, Ryan A, Rosenfeld M. Requirement for Brn-3.0 in differentiation and survival of sensory and motor neurons. Nature. 1996;384:574-7 pubmed
    ..Deletion of Brn-3.0 also alters either differentiation, migration or survival of specific central neuronal populations. ..
  20. 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. ..
  21. Yang Z, Ding K, Pan L, Deng M, Gan L. Math5 determines the competence state of retinal ganglion cell progenitors. Dev Biol. 2003;264:240-54 pubmed
  22. Ensor E, Mathews K, Payne Smith M, Latchman D. Sensory neurons from mice lacking the Brn-3b POU family transcription factor are resistant to death-inducing stimuli both in vitro and in vivo. Brain Res Mol Brain Res. 2003;117:206-12 pubmed
    ..We show that the Brn-3b transcription factor is essential for normal cell death responses in the peripheral nervous system and that in its absence neurons are resistant to a variety of death-inducing stimuli both in vitro and in vivo. ..
  23. 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
    ..Taken together, Isl1 is expressed during the maturation of and is later maintained in retinal ganglion cells and subtypes of amacrine and bipolar cells where it may function in the maintenance of these cells into adulthood. ..
  24. Budhram Mahadeo V, Bowen S, Lee S, Perez Sanchez C, Ensor E, Morris P, et al. Brn-3b enhances the pro-apoptotic effects of p53 but not its induction of cell cycle arrest by cooperating in trans-activation of bax expression. Nucleic Acids Res. 2006;34:6640-52 pubmed
    ..Thus, the ability of Brn-3b to interact with p53 and modulate Bax expression may demonstrate an important mechanism that helps to determine the fate of cells when p53 is induced. ..
  25. Shi M, Kumar S, Motajo O, Kretschmer F, Mu X, Badea T. Genetic interactions between Brn3 transcription factors in retinal ganglion cell type specification. PLoS ONE. 2013;8:e76347 pubmed publisher
    ..Previously, we described cell autonomous effects of Brn3b (Pou4f2) and Brn3a (Pou4f1) on RGC axon and dendrites development...
  26. Brown N, Patel S, Brzezinski J, Glaser T. Math5 is required for retinal ganglion cell and optic nerve formation. Development. 2001;128:2497-508 pubmed
    ..A small number of nascent RGCs are detected during embryogenesis, but these fail to develop further, suggesting that committed RGCs may also require Math5 function. ..
  27. Martin S, Mu X, Klein W. Identification of an N-terminal transcriptional activation domain within Brn3b/POU4f2. Differentiation. 2005;73:18-27 pubmed
    The POU-domain transcription factor Brn3b/ POU4f2 is an essential regulator of gene expression in mouse retinal ganglion cells...
  28. Xiang M, Gan L, Li D, Chen Z, Zhou L, O Malley B, et al. Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development. Proc Natl Acad Sci U S A. 1997;94:9445-50 pubmed
  29. Zou M, Li S, Klein W, Xiang M. Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Dev Biol. 2012;364:114-27 pubmed publisher
    ..Given the expression of the POU homeodomain transcription factors Brn3a/Pou4f1 and Brn3b/Pou4f2 in DRG and spinal cord sensory neurons, we determined the subtype specification of DRG and spinal cord sensory ..
  30. Wang S, Mu X, Bowers W, Kim D, Plas D, Crair M, et al. Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. Development. 2002;129:467-77 pubmed
    ..During retinal ganglion cell differentiation, Brn3b is expressed first, followed by Brn3a and Brn3c...
  31. de Melo J, Du G, Fonseca M, Gillespie L, Turk W, Rubenstein J, et al. Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina. Development. 2005;132:311-22 pubmed
    ..Herein, we propose a model whereby early-born RGCs are Dlx1 and Dlx2 independent, but Dlx function is necessary for terminal differentiation of late-born RGC progenitors. ..
  32. Sigulinsky C, Green E, Clark A, Levine E. Vsx2/Chx10 ensures the correct timing and magnitude of Hedgehog signaling in the mouse retina. Dev Biol. 2008;317:560-75 pubmed publisher
    ..Our results suggest that reduced Hh signaling contributes to the reduced level of RPC proliferation in the orJ retina, thereby revealing a role for Vsx2 in mediating mitogen signaling. ..
  33. Marillat V, Sabatier C, Failli V, Matsunaga E, Sotelo C, Tessier Lavigne M, et al. The slit receptor Rig-1/Robo3 controls midline crossing by hindbrain precerebellar neurons and axons. Neuron. 2004;43:69-79 pubmed
    ..These results demonstrate that Rig-1 controls the ability of both precerebellar neuron cell bodies and their axons to cross the midline. ..
  34. Bloch Gallego E, Ezan F, Tessier Lavigne M, Sotelo C. Floor plate and netrin-1 are involved in the migration and survival of inferior olivary neurons. J Neurosci. 1999;19:4407-20 pubmed
    ..They also establish a requirement for netrin-1, either directly or indirectly, for the survival of inferior olivary neurons. ..
  35. Cheng C, Chow R, Lebel M, Sakuma R, Cheung H, Thanabalasingham V, et al. The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development. Dev Biol. 2005;287:48-60 pubmed
    ..These results indicate that there are at least two distinct genetic pathways (Irx5-dependent and Vsx1-dependent) regulating the development of Type 2 and Type 3 cone bipolar cells. ..
  36. Chen S, Badea T, Hattar S. Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs. Nature. 2011;476:92-5 pubmed publisher
    ..Here we show that ipRGCs consist of distinct subpopulations that differentially express the Brn3b transcription factor, and can be functionally distinguished...
  37. 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. ..
  38. 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
    ..5 (Eisenstat et al. [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...
  39. Badea T, Cahill H, Ecker J, Hattar S, Nathans J. Distinct roles of transcription factors brn3a and brn3b in controlling the development, morphology, and function of retinal ganglion cells. Neuron. 2009;61:852-64 pubmed publisher
    ..Here we dissect the roles of the highly homologous POU-domain transcription factors Brn3a and Brn3b in retinal ganglion cell (RGC) development and function using conditional Brn3a and Brn3b alleles that permit the ..
  40. 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
    ..hierarchy because it is essential for the formation of RGCs and the expression of the immediate downstream factor Pou4f2. Based on its expression, we also proposed that Isl1, a LIM-homeodomain factor, functions in parallel with Pou4f2 ..
  41. Mao C, Wang S, Pan P, Klein W. Rewiring the retinal ganglion cell gene regulatory network: Neurod1 promotes retinal ganglion cell fate in the absence of Math5. Development. 2008;135:3379-88 pubmed publisher
    ..We conclude that, although Neurod1 and Math3 have evolved specialized functions for establishing amacrine cell fate, they are nevertheless capable of alternative functions when expressed in foreign environments. ..
  42. 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. ..
  43. Quina L, Pak W, Lanier J, Banwait P, Gratwick K, Liu Y, et al. Brn3a-expressing retinal ganglion cells project specifically to thalamocortical and collicular visual pathways. J Neurosci. 2005;25:11595-604 pubmed
    ..Brn3a is coexpressed extensively with the closely related factor Brn3b in the embryonic retina, and the effects of the loss of Brn3a in retinal development are not severe, suggesting ..
  44. Xiang M, Gan L, Zhou L, Klein W, Nathans J. Targeted deletion of the mouse POU domain gene Brn-3a causes selective loss of neurons in the brainstem and trigeminal ganglion, uncoordinated limb movement, and impaired suckling. Proc Natl Acad Sci U S A. 1996;93:11950-5 pubmed
  45. Gan L, Xiang M, Zhou L, Wagner D, Klein W, Nathans J. POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells. Proc Natl Acad Sci U S A. 1996;93:3920-5 pubmed
    ..In Brn-3b (-/-) mice other neurons within the retina and brain are minimally or not at all affected. These experiments indicate that Brn-3b plays an essential role in the development of specific ganglion cell types. ..
  46. 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 pubmed
  47. Badea T, Hua Z, Smallwood P, Williams J, Rotolo T, Ye X, et al. New mouse lines for the analysis of neuronal morphology using CreER(T)/loxP-directed sparse labeling. PLoS ONE. 2009;4:e7859 pubmed publisher
    ..The two new mouse lines described here expand the repertoire of genetically engineered mice available for controlled in vivo recombination and cell labeling using the Cre-lox system. ..
  48. Wang Y, Dakubo G, Howley P, Campsall K, Mazarolle C, Shiga S, et al. Development of normal retinal organization depends on Sonic hedgehog signaling from ganglion cells. Nat Neurosci. 2002;5:831-2 pubmed
    ..Here we show that Sonic hedgehog signaling from RGCs is required for the normal laminar organization in the vertebrate retina. ..
  49. Qiu F, Jiang H, Xiang M. A comprehensive negative regulatory program controlled by Brn3b to ensure ganglion cell specification from multipotential retinal precursors. J Neurosci. 2008;28:3392-403 pubmed publisher
    ..Here we show that the previously unsuspected POU domain transcription factor Brn3b (brain-specific homeobox/POU domain protein 3b) plays such a critical role...
  50. Badea T, Williams J, Smallwood P, Shi M, Motajo O, Nathans J. Combinatorial expression of Brn3 transcription factors in somatosensory neurons: genetic and morphologic analysis. J Neurosci. 2012;32:995-1007 pubmed publisher
    The three members of the Brn3 family of POU-domain transcription factors (Brn3a/Pou4f1, Brn3b/Pou4f2, and Brn3c/Pou4f3) are expressed in overlapping subsets of visual, auditory/vestibular, and somatosensory neurons...
  51. 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. ..
  52. Xiang M, Zhou L, Macke J, Yoshioka T, Hendry S, Eddy R, et al. The Brn-3 family of POU-domain factors: primary structure, binding specificity, and expression in subsets of retinal ganglion cells and somatosensory neurons. J Neurosci. 1995;15:4762-85 pubmed
  53. Backer S, Hidalgo Sanchez M, Offner N, Portales Casamar E, Debant A, Fort P, et al. Trio controls the mature organization of neuronal clusters in the hindbrain. J Neurosci. 2007;27:10323-32 pubmed
    ..Altogether, those results establish a link between Trio activity, the subsequent Rac1 activation, and neuronal clusters organization, as well as a possible recruitment of the Cadherin-11 adhesive receptor to form a complex with Trio. ..