Gene Symbol: Pou3f3
Description: POU domain, class 3, transcription factor 3
Alias: Brn-1, Brn1, HST011, Otf8, Skin1, urehr2, POU domain, class 3, transcription factor 3, OTF-8, brain-1, brain-specific homeobox/POU domain protein 1, oct-8, octamer-binding protein 8, octamer-binding transcription factor 8
Species: mouse
Products:     Pou3f3

Top Publications

  1. McEvilly R, de Diaz M, Schonemann M, Hooshmand F, Rosenfeld M. Transcriptional regulation of cortical neuron migration by POU domain factors. Science. 2002;295:1528-32 pubmed
  2. Chae T, Kim S, Marz K, Hanson P, Walsh C. The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate. Nat Genet. 2004;36:264-70 pubmed
    ..Apical localization of the SNARE Vamp7 is also disrupted. Thus, alpha Snap is essential for apical protein localization and cell fate determination in neuroepithelial cells. ..
  3. Sock E, Enderich J, Rosenfeld M, Wegner M. Identification of the nuclear localization signal of the POU domain protein Tst-1/Oct6. J Biol Chem. 1996;271:17512-8 pubmed
  4. Zhang J, Taylor R, La Torre A, Wilken M, Cox K, Reh T, et al. Ezh2 maintains retinal progenitor proliferation, transcriptional integrity, and the timing of late differentiation. Dev Biol. 2015;403:128-38 pubmed publisher
  5. Sumiyama K, Washio Watanabe K, Saitou N, Hayakawa T, Ueda S. Class III POU genes: generation of homopolymeric amino acid repeats under GC pressure in mammals. J Mol Evol. 1996;43:170-8 pubmed
    ..Those amino acids were encoded by triplet codons with relatively high GC content. These results suggest that the GC pressure has facilitated generation of the homopolymeric amino acid repeats. ..
  6. Welch C, Xia Y, Hong H, Stallcup M, Lusis A. Localization of the mouse glucocorticoid receptor-interacting protein 1 gene (Grip1) to proximal chromosome 1 by linkage analysis. Mamm Genome. 1997;8:620-1 pubmed
  7. Feng Y, Walsh C. Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron. 2004;44:279-93 pubmed
    ..Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex. ..
  8. Dominguez M, Ayoub A, Rakic P. POU-III transcription factors (Brn1, Brn2, and Oct6) influence neurogenesis, molecular identity, and migratory destination of upper-layer cells of the cerebral cortex. Cereb Cortex. 2013;23:2632-43 pubmed publisher
    ..POU-homeodomain transcription factors Pou3f3 and Pou3f2 (Brn1 and Brn2) are known to label postmitotic upper-layer cells, and are redundantly required for ..
  9. Stevens H, Smith K, Maragnoli M, Fagel D, Borok E, Shanabrough M, et al. Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits. J Neurosci. 2010;30:5590-602 pubmed publisher
    ..These data demonstrate that FGFR2 signaling expands the number of excitatory neurons in the mPFC and secondarily influences target neurons in subcortical stations of the limbic system. ..

More Information


  1. Catena R, Tiveron C, Ronchi A, Porta S, Ferri A, Tatangelo L, et al. Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. J Biol Chem. 2004;279:41846-57 pubmed
    ..Mutation of POU factor binding sites, able to recognize the neural factors Brn1 and Brn2, shows that these sites contribute to transgene activity in neural cells...
  2. Keimpema E, Barabas K, Morozov Y, Tortoriello G, Torii M, Cameron G, et al. Differential subcellular recruitment of monoacylglycerol lipase generates spatial specificity of 2-arachidonoyl glycerol signaling during axonal pathfinding. J Neurosci. 2010;30:13992-4007 pubmed publisher
  3. Grote D, Souabni A, Busslinger M, Bouchard M. Pax 2/8-regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney. Development. 2006;133:53-61 pubmed
    ..Together, these results define Gata3 as a key regulator of nephric duct morphogenesis and guidance in the pro/mesonephric kidney. ..
  4. Bouchard M, Grote D, Craven S, Sun Q, Steinlein P, Busslinger M. Identification of Pax2-regulated genes by expression profiling of the mid-hindbrain organizer region. Development. 2005;132:2633-43 pubmed
    ..These genes code for the transcription factors En2 and Brn1 (Pou3f3), the intracellular signaling modifiers Sef and Tapp1, and the non-coding RNA Ncrms...
  5. Cubelos B, Sebastián Serrano A, Kim S, Moreno Ortiz C, Redondo J, Walsh C, et al. Cux-2 controls the proliferation of neuronal intermediate precursors of the cortical subventricular zone. Cereb Cortex. 2008;18:1758-70 pubmed
    ..Our results point to Cux-2 as a key element in the control of the proliferation rates of the SVZ precursors and the number of upper cortical neurons, without altering the number of deep cortical layers. ..
  6. Hara Y, Rovescalli A, Kim Y, Nirenberg M. Structure and evolution of four POU domain genes expressed in mouse brain. Proc Natl Acad Sci U S A. 1992;89:3280-4 pubmed
    ..Additional duplications of the ancestral class III POU domain gene (or mRNA) would create the Brain-1, Brain-2, Brain-4, and Scip genes. ..
  7. Westerlund N, Zdrojewska J, Padzik A, Komulainen E, Björkblom B, Rannikko E, et al. Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate. Nat Neurosci. 2011;14:305-13 pubmed publisher
    ..These findings indicate that the phosphorylation of SCG10 by JNK1 is a fundamental mechanism that governs the transition from the multipolar stage and the rate of neuronal cell movement during cortical development. ..
  8. Lake B, Sokol S. Strabismus regulates asymmetric cell divisions and cell fate determination in the mouse brain. J Cell Biol. 2009;185:59-66 pubmed publisher
    ..These findings suggest that Stbm/Vangl2 functions to maintain cortical progenitors and regulates mitotic spindle orientation during asymmetric divisions in the vertebrate brain. ..
  9. Mistri T, Devasia A, Chu L, Ng W, Halbritter F, Colby D, et al. Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells. EMBO Rep. 2015;16:1177-91 pubmed publisher
    ..Neural stem cells (NSCs) lack Oct4 but express Sox2 and class III POU-TFs Oct6, Brn1 and Brn2. This raises the question of how Sox2 interacts with POU-TFs to transcriptionally specify ESCs versus NSCs...
  10. Labosky P, Winnier G, Jetton T, Hargett L, Ryan A, Rosenfeld M, et al. The winged helix gene, Mf3, is required for normal development of the diencephalon and midbrain, postnatal growth and the milk-ejection reflex. Development. 1997;124:1263-74 pubmed
    ..These results provide evidence that Mf3 is required for normal hypothalamus development and suggest that Mf3 may play a role in postnatal growth and lactation. ..
  11. Schonemann M, Ryan A, McEvilly R, O Connell S, Arias C, Kalla K, et al. Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2. Genes Dev. 1995;9:3122-35 pubmed
  12. Wolf M, Lommes P, Sock E, Reiprich S, Friedrich R, Kriesch J, et al. Replacement of related POU transcription factors leads to severe defects in mouse forebrain development. Dev Biol. 2009;332:418-28 pubmed publisher
    ..The extent of functional equivalence between related transcription factors is thus strongly dependent on the analyzed tissue. ..
  13. Nakamura A, Swahari V, Plestant C, Smith I, McCoy E, SMITH S, et al. Bcl-xL Is Essential for the Survival and Function of Differentiated Neurons in the Cortex That Control Complex Behaviors. J Neurosci. 2016;36:5448-61 pubmed publisher
  14. Sugitani Y, Nakai S, Minowa O, Nishi M, Jishage K, Kawano H, et al. Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons. Genes Dev. 2002;16:1760-5 pubmed
    ..These data indicate that Brn-1 and Brn-2 share roles in the production and positioning of neocortical neuron development. ..
  15. Jin Z, Liu L, Bian W, Chen Y, Xu G, Cheng L, et al. Different transcription factors regulate nestin gene expression during P19 cell neural differentiation and central nervous system development. J Biol Chem. 2009;284:8160-73 pubmed publisher
    ..Sox2 and SF1 may mediate basal nestin expression in undifferentiated P19EC cells, whereas Sox2, Brn1, and Brn2 bind to the enhancer in P19 neural progenitor cells...
  16. Nielsen J, Nielsen F, Ismail R, Noraberg J, Jensen N. Hippocampus-like corticoneurogenesis induced by two isoforms of the BTB-zinc finger gene Zbtb20 in mice. Development. 2007;134:1133-40 pubmed
    ..Overall, our in vivo data suggest that Zbtb20 functions as a molecular switch for a pathway that induces invariant pyramidal neuron morphogenesis and suppression of cell fate transitions in newborn neurons. ..
  17. Nakamura K, Kosugi I, Lee D, Hafner A, Sinclair D, Ryo A, et al. Prolyl isomerase Pin1 regulates neuronal differentiation via ?-catenin. Mol Cell Biol. 2012;32:2966-78 pubmed publisher
  18. Mutai H, Nagashima R, Sugitani Y, Noda T, Fujii M, Matsunaga T. Expression of Pou3f3/Brn-1 and its genomic methylation in developing auditory epithelium. Dev Neurobiol. 2009;69:913-30 pubmed publisher
    ..An AIMS fragment was mapped to the 3'-flanking region of Pou3f3/Brn-1...
  19. Kobayashi A, Kwan K, Carroll T, McMahon A, Mendelsohn C, Behringer R. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development. 2005;132:2809-23 pubmed
    ..We also demonstrate that the nephric duct is essential for the elongation and maintenance of the adjacent Mullerian duct, the anlage of the female reproductive tract. ..
  20. Kuhlbrodt K, Herbarth B, Sock E, Enderich J, Hermans Borgmeyer I, Wegner M. Cooperative function of POU proteins and SOX proteins in glial cells. J Biol Chem. 1998;273:16050-7 pubmed
    ..Our data suggest the existence of a specific code in which POU proteins require specific Sox proteins to exhibit cooperative effects in glial cells. ..
  21. Malik K, Jaffe H, Brady J, Young W. The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U. Brain Res Mol Brain Res. 1997;45:99-107 pubmed
    ..This result suggests another mechanism by which a POU protein can influence gene expression: by facilitating the processing of pre-mRNA whose transcription it has stimulated. ..
  22. Rieger A, Kemter E, Kumar S, Popper B, Aigner B, Wolf E, et al. Missense Mutation of POU Domain Class 3 Transcription Factor 3 in Pou3f3L423P Mice Causes Reduced Nephron Number and Impaired Development of the Thick Ascending Limb of the Loop of Henle. PLoS ONE. 2016;11:e0158977 pubmed publisher
    During nephrogenesis, POU domain class 3 transcription factor 3 (POU3F3 aka BRN1) is critically involved in development of distinct nephron segments, including the thick ascending limb of the loop of Henle (TAL)...
  23. Ka M, Jung E, Mueller U, Kim W. MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling. Dev Biol. 2014;395:4-18 pubmed publisher
    ..Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. ..
  24. Tian Y, Lei L, Minden A. A key role for Pak4 in proliferation and differentiation of neural progenitor cells. Dev Biol. 2011;353:206-16 pubmed publisher
    ..These results suggest that Pak4 plays a critical role in the regulation of neural progenitor cell proliferation and in establishing the foundation for development of the adult brain. ..
  25. Lizarraga S, Margossian S, Harris M, Campagna D, Han A, Blevins S, et al. Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors. Development. 2010;137:1907-17 pubmed publisher
    ..Our findings suggest that the reduction in brain size observed in humans with mutations in CDK5RAP2 is associated with impaired centrosomal function and with changes in mitotic spindle orientation during progenitor proliferation. ..
  26. 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
  27. Yokota Y, Kim W, Chen Y, Wang X, Stanco A, Komuro Y, et al. The adenomatous polyposis coli protein is an essential regulator of radial glial polarity and construction of the cerebral cortex. Neuron. 2009;61:42-56 pubmed publisher
    ..Thus, APC is an essential regulator of radial glial polarity and is critical for the construction of cerebral cortex in mammals. ..
  28. Mulder J, Spence L, Tortoriello G, DiNieri J, Uhlen M, Shui B, et al. Secretagogin is a Ca2+-binding protein identifying prospective extended amygdala neurons in the developing mammalian telencephalon. Eur J Neurosci. 2010;31:2166-77 pubmed publisher
    ..Overall, our findings emphasize the developmentally shared origins of neurons populating the extended amygdala, and suggest that secretagogin can be relevant to the generation of functional modalities in specific neuronal circuitries. ..
  29. Herrick T, Cooper J. High affinity binding of Dab1 to Reelin receptors promotes normal positioning of upper layer cortical plate neurons. Brain Res Mol Brain Res. 2004;126:121-8 pubmed
    ..The Dab1(F158V) allele adds to a series of Dab1 alleles that demonstrates cell type-specific variation in the Reelin-Dab1 pathway. ..
  30. Bildsoe H, Loebel D, Jones V, Chen Y, Behringer R, Tam P. Requirement for Twist1 in frontonasal and skull vault development in the mouse embryo. Dev Biol. 2009;331:176-88 pubmed publisher
    ..In contrast, the formation of other mesodermal skeletal derivatives such as the occipital bones and most of the chondrocranium are not affected by the loss of Twist1 in the neural crest cells. ..
  31. Jossin Y, Lee M, Klezovitch O, Kon E, Cossard A, Lien W, et al. Llgl1 Connects Cell Polarity with Cell-Cell Adhesion in Embryonic Neural Stem Cells. Dev Cell. 2017;41:481-495.e5 pubmed publisher
    ..These findings reveal a mechanism responsible for the physical and functional connection between cell polarity and cell-cell adhesion machineries in mammalian cells. ..
  32. Friedrich R, Schlierf B, Tamm E, Bösl M, Wegner M. The class III POU domain protein Brn-1 can fully replace the related Oct-6 during schwann cell development and myelination. Mol Cell Biol. 2005;25:1821-9 pubmed
    ..Similar to Oct-6, Brn-1 down-regulated its own expression at later stages of myelination. Thus, class III POU domain proteins can fully replace each other in Schwann cell development. ..
  33. Kuo G, Arnaud L, Kronstad O Brien P, Cooper J. Absence of Fyn and Src causes a reeler-like phenotype. J Neurosci. 2005;25:8578-86 pubmed
    ..This implies that Src and Fyn are needed for Reelin-dependent events during brain development...
  34. SAMUELS I, Karlo J, Faruzzi A, Pickering K, Herrup K, Sweatt J, et al. Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function. J Neurosci. 2008;28:6983-95 pubmed publisher
    ..These findings demonstrate an important role for ERK2 in cellular proliferation and differentiation during neural development as well as in cognition and memory formation. ..
  35. Weimer J, Yokota Y, Stanco A, Stumpo D, Blackshear P, Anton E. MARCKS modulates radial progenitor placement, proliferation and organization in the developing cerebral cortex. Development. 2009;136:2965-75 pubmed publisher
  36. Nakagawa N, Yagi H, Kato K, Takematsu H, Oka S. Ectopic clustering of Cajal-Retzius and subplate cells is an initial pathological feature in Pomgnt2-knockout mice, a model of dystroglycanopathy. Sci Rep. 2015;5:11163 pubmed publisher
    ..Our findings demonstrate the initial pathological events in dystroglycanopathy mice and contribute to our understanding of how dystroglycan dysfunction affects brain development and progresses to cobblestone lissencephaly. ..
  37. Castro D, Skowronska Krawczyk D, Armant O, Donaldson I, Parras C, Hunt C, et al. Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif. Dev Cell. 2006;11:831-44 pubmed
    ..Here, we demonstrate that the proneural protein Mash1 and the POU proteins Brn1 and Brn2 interact on the promoter of the Notch ligand Delta1 and synergistically activate Delta1 transcription, a ..
  38. Basta J, Robbins L, Denner D, Kolar G, Rauchman M. A Sall1-NuRD interaction regulates multipotent nephron progenitors and is required for loop of Henle formation. Development. 2017;144:3080-3094 pubmed publisher
    ..These findings highlight an important function of Sall1-NuRD interaction in the regulation of Six2-positive multipotent renal progenitor cells and formation of the loop of Henle. ..
  39. Tavares A, Cox T, Maxson R, Ford H, Clouthier D. Negative regulation of endothelin signaling by SIX1 is required for proper maxillary development. Development. 2017;144:2021-2031 pubmed publisher
    ..Together, our results illustrate that SIX1 is the central mediator of dorsal mandibular arch identity, thus ensuring separation of bone development between the upper and lower jaws. ..
  40. Capecchi M, Pozner A. ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination. Nat Commun. 2015;6:8763 pubmed publisher
    ..Thus, we reveal a novel function of ASPM in mediating the tightly coordinated Ubiquitin- Cyclin E- Retinoblastoma- E2F bistable-signalling pathway controlling restriction point progression and stem cell maintenance. ..
  41. Iwafuchi Doi M, Matsuda K, Murakami K, Niwa H, Tesar P, Aruga J, et al. Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells. Development. 2012;139:3926-37 pubmed publisher
    ..The direct interaction of these factors with enhancers of Otx2, Hesx1 and Sox2 genes was demonstrated. Thus, a combination of regulatory processes that suppresses non-ANP lineages and promotes neural plate development determines the ANP...
  42. Pucilowska J, Vithayathil J, Tavares E, Kelly C, Karlo J, Landreth G. The 16p11.2 deletion mouse model of autism exhibits altered cortical progenitor proliferation and brain cytoarchitecture linked to the ERK MAPK pathway. J Neurosci. 2015;35:3190-200 pubmed publisher
    ..2del mice exhibit anxiety-like behaviors and impaired memory. Our findings provide evidence of ERK dysregulation, developmental abnormalities in neurogenesis, and behavioral impairment associated with the 16p11.2 chromosomal deletion. ..
  43. Sánchez Camacho C, Ortega J, Ocaña I, Alcantara S, Bovolenta P. Appropriate Bmp7 levels are required for the differentiation of midline guidepost cells involved in corpus callosum formation. Dev Neurobiol. 2011;71:337-50 pubmed publisher
    ..Together, these results indicate that Bmp7 is indirectly required for corpus callosum formation by controlling the timely differentiation of its guidepost cells. ..
  44. Fontaine R, Cases O, Lelievre V, Mesples B, Renauld J, Loron G, et al. IL-9/IL-9 receptor signaling selectively protects cortical neurons against developmental apoptosis. Cell Death Differ. 2008;15:1542-52 pubmed publisher
    ..Together, these data suggest that IL-9/IL-9 receptor signaling pathway represents a novel endogenous antiapoptotic mechanism for cortical neurons by controlling JAK/STAT and Bax levels. ..
  45. Pucilowska J, Puzerey P, Karlo J, Galán R, Landreth G. Disrupted ERK signaling during cortical development leads to abnormal progenitor proliferation, neuronal and network excitability and behavior, modeling human neuro-cardio-facial-cutaneous and related syndromes. J Neurosci. 2012;32:8663-77 pubmed publisher
    ..This study provides a novel mechanistic insight into the basis of cortical malformation which may provide a potential link to cognitive deficits in individuals with altered ERK activity. ..
  46. Reggiani L, Raciti D, Airik R, Kispert A, Brändli A. The prepattern transcription factor Irx3 directs nephron segment identity. Genes Dev. 2007;21:2358-70 pubmed
    ..Taken together, irx3 is the first gene known to be necessary and sufficient to specify nephron segment fate in vivo. ..
  47. Worzfeld T, Swiercz J, Sentürk A, Genz B, Korostylev A, Deng S, et al. Genetic dissection of plexin signaling in vivo. Proc Natl Acad Sci U S A. 2014;111:2194-9 pubmed publisher
    ..Our genetic analyses uncover the in vivo context-dependence and functional specificity of individual plexin-mediated signaling pathways during development. ..
  48. Kumar S, Rathkolb B, Kemter E, Sabrautzki S, Michel D, Adler T, et al. Generation and Standardized, Systemic Phenotypic Analysis of Pou3f3L423P Mutant Mice. PLoS ONE. 2016;11:e0150472 pubmed publisher
    ..The phenotypically recessive mutant line HST011 was established and further analyzed...
  49. Aigner B, Rathkolb B, Herbach N, Kemter E, Schessl C, Klaften M, et al. Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models. Am J Physiol Renal Physiol. 2007;292:F1560-7 pubmed
  50. Lee H, Inoue T, Sasaki J, Kubo T, Matsuda S, Nakasaki Y, et al. LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice. Mol Biol Cell. 2012;23:4689-700 pubmed publisher
    ..Taken together, these results demonstrate that AA-containing PI/PI phosphates play an important role in normal cortical lamination during brain development in mice. ..
  51. Chen L, Liao G, Waclaw R, Burns K, Linquist D, Campbell K, et al. Rac1 controls the formation of midline commissures and the competency of tangential migration in ventral telencephalic neurons. J Neurosci. 2007;27:3884-93 pubmed
    ..Moreover, they indicate that Rac1 has a critical role in axon guidance and in acquisition of migratory competency during differentiation of the progenitors for the ventral telencephalon-derived interneurons. ..
  52. Hartman H, Lai H, Patterson L. Cessation of renal morphogenesis in mice. Dev Biol. 2007;310:379-87 pubmed
    ..These results suggest that the sequence of events leading to disruption of the cycle of branching morphogenesis and nephrogenesis began with the loss of mesenchyme that resulted from its conversion into nephrons. ..
  53. Chakrabarti L, Galdzicki Z, Haydar T. Defects in embryonic neurogenesis and initial synapse formation in the forebrain of the Ts65Dn mouse model of Down syndrome. J Neurosci. 2007;27:11483-95 pubmed
    ..The early prenatal period is therefore an important new window for possible therapeutic amelioration of the cognitive symptoms in DS. ..