Genomes and Genes
Gene Symbol: Pou4f1
Description: POU domain, class 4, transcription factor 1
Alias: Brn-3, Brn-3.0, Brn3, Brn3.0, Brn3a, E130119J07Rik, POU domain, class 4, transcription factor 1, brain-3A, brain-specific homeobox/POU domain protein 3A, brn-3A
- Hippenmeyer S, Vrieseling E, Sigrist M, Portmann T, Laengle C, Ladle D, et al. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 2005;3:e159 pubmed..Together, our findings indicate that DRG sensory neurons exhibit a temporal developmental switch that can be revealed by distinct responses to ETS transcription factor signaling at sequential steps of neuronal maturation. ..
- Hudson C, Podesta J, Henderson D, Latchman D, Budhram Mahadeo V. Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis. J Neurosci Res. 2004;78:803-14 pubmed..Thus, p53 is expressed in neuronal cells undergoing differentiation as well as apoptosis. Interaction with Brn-3a in sensory neurons may be critical for modulating p53-mediated gene expression and hence cell fate. ..
- Peltopuro P, Kala K, Partanen J. Distinct requirements for Ascl1 in subpopulations of midbrain GABAergic neurons. Dev Biol. 2010;343:63-70 pubmed publisher..Also, our results have implications on understanding the origins of the various midbrain GABAergic neuron groups in the embryonic neuroepithelium. ..
- Sun Y, Dykes I, Liang X, Eng S, Evans S, Turner E. A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nat Neurosci. 2008;11:1283-93 pubmed publisher..Together these results establish a central role for Islet1 in the transition from sensory neurogenesis to subtype specification. ..
- 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...
- Andersson E, Jensen J, Parmar M, Guillemot F, Bjorklund A. Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2. Development. 2006;133:507-16 pubmed
- Sonnenberg Riethmacher E, Miehe M, Stolt C, Goerich D, Wegner M, Riethmacher D. Development and degeneration of dorsal root ganglia in the absence of the HMG-domain transcription factor Sox10. Mech Dev. 2001;109:253-65 pubmed..5 and E 11.5). We show that both increased apoptosis as well as decreased proliferation of neural crest cells contribute to the observed hypomorphism. ..
- 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. ..
- Montelius A, Marmigere F, Baudet C, Aquino J, Enerback S, Ernfors P. Emergence of the sensory nervous system as defined by Foxs1 expression. Differentiation. 2007;75:404-17 pubmed..of the Foxs1(-)/Sox10(+) precursors occurred within the condensed DRG starting with neurogenin-1 (Ngn1) and Brn3a expression...
- 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
- 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. ..
- Calissano M, Latchman D. Functional interaction between the small GTP-binding protein Rin and the N-terminal of Brn-3a transcription factor. Oncogene. 2003;22:5408-14 pubmed..In this work, we describe the evidence for a functional interaction between Brn-3a and Rin and demonstrate the role of Rin in modulating the activation of the Brn-3a regulated egr-1 promoter by the N-terminal domain of Brn-3a. ..
- Ichikawa H, Schulz S, Hollt V, Mo Z, Xiang M, Sugimoto T. Effect of Brn-3a deficiency on primary nociceptors in the trigeminal ganglion. Neurosci Res. 2005;51:445-51 pubmed..The present study suggests that Brn-3a deficiency may have effects on the survival of trigeminal nociceptors and their expression of some neurochemical substances. ..
- 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
- Nakatani T, Minaki Y, Kumai M, Ono Y. Helt determines GABAergic over glutamatergic neuronal fate by repressing Ngn genes in the developing mesencephalon. Development. 2007;134:2783-93 pubmed
- Xiang M. Requirement for Brn-3b in early differentiation of postmitotic retinal ganglion cell precursors. Dev Biol. 1998;197:155-69 pubmed
- Hudson C, Morris P, Latchman D, Budhram Mahadeo V. Brn-3a transcription factor blocks p53-mediated activation of proapoptotic target genes Noxa and Bax in vitro and in vivo to determine cell fate. J Biol Chem. 2005;280:11851-8 pubmed..These results support a crucial role for Brn-3a in determining the pathway taken by p53 when co-expressed during development and thus in controlling the fate of these cells. ..
- Eng S, Lanier J, Fedtsova N, Turner E. Coordinated regulation of gene expression by Brn3a in developing sensory ganglia. Development. 2004;131:3859-70 pubmedMice lacking the POU-domain transcription factor Brn3a exhibit marked defects in sensory axon growth and abnormal sensory apoptosis...
- Faulkes D, Ensor E, Le Rouzic E, Latchman D. Distinct domains of Brn-3a regulate apoptosis and neurite outgrowth in vivo. Neuroreport. 2004;15:1421-5 pubmed..Hence the two naturally occurring forms of Brn-3a, which either contain or lack the N-terminal domain, are likely to play distinct roles in the nervous system. ..
- Agarwala S, Ragsdale C. A role for midbrain arcs in nucleogenesis. Development. 2002;129:5779-88 pubmed..Taken together, these findings suggest that arcs represent a patterning mechanism by which midbrain progenitor cells are allocated to specific nuclear fates. ..
- Zhong J, Li X, McNamee C, Chen A, Baccarini M, Snider W. Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo. Nat Neurosci. 2007;10:598-607 pubmed..We conclude that Raf function is crucial for several aspects of DRG neuron development, including differentiation and axon growth. ..
- Dykes I, Tempest L, Lee S, Turner E. Brn3a and Islet1 act epistatically to regulate the gene expression program of sensory differentiation. J Neurosci. 2011;31:9789-99 pubmed publisher..of the trigeminal ganglion (TG) and dorsal root ganglia (DRG) coexpress the homeodomain transcription factors Brn3a and Islet1, and past work has revealed partially overlapping programs of gene expression downstream of these ..
- Eng S, Gratwick K, Rhee J, Fedtsova N, Gan L, Turner E. Defects in sensory axon growth precede neuronal death in Brn3a-deficient mice. J Neurosci. 2001;21:541-9 pubmedb>Brn3a/Brn-3.0 is a POU-domain transcription factor expressed in primary sensory neurons of the cranial and dorsal root ganglia and in specific neurons in the caudal CNS...
- Kriks S, Lanuza G, Mizuguchi R, Nakafuku M, Goulding M. Gsh2 is required for the repression of Ngn1 and specification of dorsal interneuron fate in the spinal cord. Development. 2005;132:2991-3002 pubmed..Our results provide evidence that genetic interactions involving repression of Ngn1 by Gsh2 promote the differentiation of dI3 neurons from class A progenitors. ..
- Huang E, Liu W, Fritzsch B, Bianchi L, Reichardt L, Xiang M. Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons. Development. 2001;128:2421-32 pubmedThe POU domain transcription factors Brn3a, Brn3b and Brn3c are required for the proper development of sensory ganglia, retinal ganglion cells, and inner ear hair cells, respectively...
- 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. ..
- Perez Balaguer A, Puelles E, Wurst W, Martinez S. Shh dependent and independent maintenance of basal midbrain. Mech Dev. 2009;126:301-13 pubmed publisher..Based on our results and recently published data, we suggest the existence of a specific genetic pathway for the specification of the mesencephalic red nucleus. Foxa2 could be the candidate gene that might control this genetic pathway. ..
- Gowan K, Helms A, Hunsaker T, Collisson T, Ebert P, Odom R, et al. Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons. Neuron. 2001;31:219-32 pubmed..Together, the data suggest that although Math1 and Ngn1 appear to be redundant with respect to neurogenesis, they have distinct functions in specifying neuronal subtype in the dorsal neural tube. ..
- Lin W, Metzakopian E, Mavromatakis Y, Gao N, Balaskas N, Sasaki H, et al. Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Dev Biol. 2009;333:386-96 pubmed publisher..Our data therefore provide new insights into the specification and differentiation of mesodiencephalic dopaminergic neurons and identifies Foxa1 and Foxa2 as essential regulators in these processes. ..
- Joksimovic M, Anderegg A, Roy A, Campochiaro L, Yun B, Kittappa R, et al. Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools. Proc Natl Acad Sci U S A. 2009;106:19185-90 pubmed publisher..This refined ontogenetic definition will expand understanding of dopamine neuron biology and selective susceptibility, and will impact stem cell-derived therapies and models for PD. ..
- 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 publisherThe 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...
- Ichikawa H, Yamaai T, Jacobowitz D, Mo Z, Xiang M, Sugimoto T. Effect of Brn-3a deficiency on parvalbumin-, calbindin D-28k-, calretinin- and calcitonin gene-related peptide-immunoreactive primary sensory neurons in the trigeminal ganglion. Neuroscience. 2002;113:537-46 pubmed..Taken together, our data suggest that Brn-3a deficiency has effects on the expression of neurochemical substances in the trigeminal ganglion. ..
- 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. ..
- 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. ..
- Gross M, Dottori M, Goulding M. Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron. 2002;34:535-49 pubmed..Lbx1, therefore, plays a critical role in the development of sensory pathways in the spinal cord that relay pain and touch. ..
- 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. ..
- 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. ..
- Thomas G, Faulkes D, Gascoyne D, Latchman D. EWS differentially activates transcription of the Brn-3a long and short isoform mRNAs from distinct promoters. Biochem Biophys Res Commun. 2004;318:1045-51 pubmed..The implications of these results are discussed in terms of the functional role of EWS and the distinct functional activities of the two isoforms of Brn-3a. ..
- 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 ..
- 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 ..
- Wiggins A, Wei G, Doxakis E, Wong C, Tang A, Zang K, et al. Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival. J Cell Biol. 2004;167:257-67 pubmedThe Pit1-Oct1-Unc86 domain (POU domain) transcription factor Brn3a controls sensory neuron survival by regulating the expression of Trk receptors and members of the Bcl-2 family...
- Mo Z, Li S, Yang X, Xiang M. Role of the Barhl2 homeobox gene in the specification of glycinergic amacrine cells. Development. 2004;131:1607-18 pubmed..Taken together, our data suggest that Barhl2 may function to specify the identity of glycinergic amacrine cells from competent progenitors during retinogenesis. ..
- Trieu M, Ma A, Eng S, Fedtsova N, Turner E. Direct autoregulation and gene dosage compensation by POU-domain transcription factor Brn3a. Development. 2003;130:111-21 pubmedb>Brn3a is a POU-domain transcription factor expressed in peripheral sensory neurons and in specific interneurons of the caudal CNS...
- 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...
- 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
- Guo C, Qiu H, Huang Y, Chen H, Yang R, Chen S, et al. Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice. Development. 2007;134:317-25 pubmed
- Mizuhara E, Nakatani T, Minaki Y, Sakamoto Y, Ono Y. Corl1, a novel neuronal lineage-specific transcriptional corepressor for the homeodomain transcription factor Lbx1. J Biol Chem. 2005;280:3645-55 pubmed..Identification of a novel transcriptional corepressor with neuronal subtype-restricted expression might provide insights into the mechanisms of cell fate determination in neurons. ..
- Mavromatakis Y, Lin W, Metzakopian E, Ferri A, Yan C, Sasaki H, et al. Foxa1 and Foxa2 positively and negatively regulate Shh signalling to specify ventral midbrain progenitor identity. Mech Dev. 2011;128:90-103 pubmed publisher..Altogether, these data indicate that Foxa1 and Foxa2 contribute to the specification of ventral midbrain progenitor identity by regulating Shh signalling in a positive and negative manner. ..
- 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. ..
- Lei L, Zhou J, Lin L, Parada L. Brn3a and Klf7 cooperate to control TrkA expression in sensory neurons. Dev Biol. 2006;300:758-69 pubmedThe zinc finger protein Klf7 and POU homeodomain protein Brn3a are each required for efficient transcription of TrkA in primary sensory neurons...
- 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. ..
- 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. ..