Journal
DEVELOPMENT
Volume 132, Issue 4, Pages 703-712Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.01646
Keywords
Brn3; POU-domain; retina; neurogenesis; retinal ganglion cells; transcription factors; Pou4f
Categories
Funding
- NEI NIH HHS [R01 EY015551, EY013426, R01 EY013426-02, R01 EY013426, EY015551, R01 EY015551-01] Funding Source: Medline
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POU-domain transcription factors play essential roles in cell proliferation and differentiation. Previous studies have shown that targeted deletion of each of the three POU-domain Brn3 factors in mice leads to the developmental failure and apoptosis of a unique set of sensory neurons in retina, dorsal root ganglia, trigeminal ganglia and inner ear. The specific defects associated with the removal of each Brn3 gene closely reflect their characteristic spatiotemporal expression patterns. Nevertheless, it remains elusive whether Brn3 factors are functionally equivalent and act through a common molecular mechanism to regulate the development and survival of these sensory neurons. By knocking-in Brn3a (Brn3a(ki)) into the Brn3b locus, we showed here that Brn3a(ki) was expressed in a spatiotemporal manner identical to that of endogenous Brn3b. In addition, Brn3a(ki) functionally restored the normal development and survival of retinal ganglion cells (RGCs) in the absence of Brn3b and fully reinstated the early developmental expression profiles of Brn3b downstream target genes in retina. These results indicate that Brn3 factors are functionally equal and that their unique roles in neurogenesis are determined by the distinctive Brn3 spatiotemporal expression patterns.
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