Pou4Brn3

Pou4Brn3 refers to the vertebrate Brn-3/POU4 subfamily of transcription factors. It encompasses three genes: Pou4f1 (Brn-3a), Pou4f2 (Brn-3b), and Pou4f3 (Brn-3c). These proteins are part of the POU family and share a bipartite POU domain that enables DNA binding to regulatory regions. They function as neural-specific transcription factors involved in the development and maintenance of post-mitotic neurons.

Expression of Brn-3/POU4 factors is enriched in neurons, notably retinal ganglion cells (RGCs) and various sensory neurons such as dorsal root ganglion neurons. They regulate gene expression programs that influence neuronal differentiation, axon growth, and survival. In mouse models, loss of Pou4f2 (Brn-3b) reduces RGC numbers and disrupts axon targeting, while Pou4f1 (Brn-3a) contributes to later differentiation and maintenance, and Pou4f3 (Brn-3c) is essential for auditory hair cell development and function.

Mechanistically, Brn-3/POU4 proteins act as transcription factors that bind DNA sequences in target gene regulatory regions and operate in combination with other transcription factors to specify neuronal identities. They contribute to cell-type–specific gene networks in the retina and inner ear and are commonly used as markers for retinal lineage in developmental studies and lineage tracing.

Evolutionarily, the Brn-3/POU4 family is conserved across jawed vertebrates. The factors have been studied in multiple model organisms, advancing understanding of retinal development, sensory neuron differentiation, and neuroprotection. Aberrant expression or function of these factors is associated with impaired neuronal development or sensory system pathology, underscoring their significance in neurobiology.