Disease relevance of Pou4f2

• Taken together, our findings demonstrate a continuous requirement for Wt1 in normal retina formation with a critical role in Pou4f2-dependent ganglion cell differentiation [1].
• The Wilms' tumor suppressor Wt1 encodes a transcriptional activator of the class IV POU-domain factor Pou4f2 (Brn-3b) [2].
• Consistent with our previous observations of increased Pou4f2 mRNA in stably Wt1-transfeced HEK293 cells [EMBO J. 21 (2002) 1398], endogenous Pou4f2 was also elevated at the protein level in the HEK293 transfectants as well as in U2OS osteosarcoma cells that expressed an inducible Wt1 isoform [2].
• Brn-3.2 exhibits DNA binding properties similar to those of Brn-3.0, but its expression is uniquely regulated by retinoic acid in teratocarcinoma and neuroblastoma cells [3].

High impact information on Pou4f2

• Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development [4].
• Deletion of the Brn-3.2 gene causes the loss of most retinal ganglion cells, defining distinct ganglion cell populations [4].
• Members of one such family, the class IV POU domain transcription factor Brn-3.0, and two highly related factors Brn-3.1 and Brn-3.2, are differentially expressed in the developing and mature mammalian nervous system [5].
• Using representational difference analysis, we identified Brn-3.2 gene targets likely to act on axon guidance at the levels of transcription, cell-cell interaction, and signal transduction, including the actin-binding LIM domain protein abLIM [6].
• We report that the murine POU domain transcription factor Brn-3.2 regulates pathfinding in retinal ganglion cell (RGC) axons at multiple points along their pathways and the establishment of topographic order in the superior colliculus [6].

Biological context of Pou4f2

• Forced expression of Wt1 in cultured cells causes an up-regulation of Pou4f2 mRNA [1].
• 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 [3].
• 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 [7].
• At later developmental stages, additional alterations in gene expression were secondary consequences of aberrant RGC differentiation caused by the absence of Brn3b [8].
• However, Brn-3b was essential for the normal differentiation of retinal ganglion cells; without it, the cells underwent enhanced apoptosis [9].

Anatomical context of Pou4f2

• By contrast, temporal and spatial expression of Pou4f2 and Pax6 in developing ganglion and amacrine cells and PNA and blue opsin in developing cone cells was relatively normal in the mutant [10].
• Double-immunofluorescent labeling revealed co-expression of Pou4f2 and Wt1 in glomerular podocytes of adult kidney and in developing retinal ganglion cells of mouse embryos [2].
• To examine the role of Brn3c in retinal ganglion cell development, we generated Brn3b/Brn3c double knockout mice and analyzed their retinas and optic chiasms [11].
• Rostral to the midbrain, Brn-3.2 and Brn-3.0 exhibit nonoverlapping patterns of expression, suggesting divergence of gene function in more recently evolved structures [3].
• Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid [3].

Associations of Pou4f2 with chemical compounds

• Here we have altered a single isoleucine residue in the POU homeodomain of Brn-3b to the valine residue found at the equivalent position in Brn-3a [12].

Regulatory relationships of Pou4f2

• Transient co-transfection of a Wt1 expression construct activated a Pou4f2 promoter-reporter construct approximately 4-fold [2].

Other interactions of Pou4f2

• We find that Brn3b(l) and Brn3b(s), the two isoforms encoded by the Brn3b gene, as well as Brn3a and Brn3c all have similar DNA-binding and transactivating activities [13].
• In conclusion, we identified Pou4f2 as a novel downstream target gene of Wt1 [2].
• We found that Brn3b influenced gene expression in non RGCs of the retina by controlling the expression of secreted signaling molecules such as sonic hedgehog and myostatin/Gdf8 [8].
• Screening with a microarray containing 864 cDNA clones using wild-type and brn-3b (-/-) retinal cDNA probes revealed a potential regulatory linkage between the transcription factor Brn-3b and expression of GAP-43, a protein associated with axon growth [14].

Analytical, diagnostic and therapeutic context of Pou4f2

• At E14.5, we identified 87 genes whose expression was significantly altered in the absence of Brn3b and verified the results by real-time PCR and in situ hybridization [8].
• We have used a quantitative RT-PCR approach to determine the levels of Brn3a and Brn3b POU domain transcription factor mRNAs in the developing mouse trigeminal ganglion from E10 to E18 [15].

References