May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Equivalent Roles of Brn–3 POU–Domain Transcription Factors in Mouse Retinal Neurogenesis
Author Affiliations & Notes
  • L. Gan
    Center for Aging and Developmental Biology, Univ of Rochester, Rochester, NY
  • L. Pan
    Center for Aging and Developmental Biology, Univ of Rochester, Rochester, NY
  • Z. Yang
    Center for Aging and Developmental Biology, Univ of Rochester, Rochester, NY
  • Footnotes
    Commercial Relationships  L. Gan, None; L. Pan, None; Z. Yang, None.
  • Footnotes
    Support  EY013426
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 703. doi:
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      L. Gan, L. Pan, Z. Yang; Equivalent Roles of Brn–3 POU–Domain Transcription Factors in Mouse Retinal Neurogenesis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):703.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Targeted mutagenesis studies have shown that deletion of each of the three POU–domain Brn–3 factors (Brn–3a, Brn–3b and Brn–3c) in mice leads to the failure in differentiation and programmed cell death of a unique set of sensory neurons closely reflecting their distinctive spatiotemporal expression patterns. Nevertheless, it remains elusive whether Brn–3 factors act through a common molecular mechanism to regulate the development and survival of sensory neurons. The purpose of the present study was to test the functional equivalence of Brn–3 factors in vivo and to identify and characterize the shared genetic pathway in regulating the development and survival of sensory neurons. Methods: brn–3a cDNA was knocked into brn–3b locus in a gene replacement experiment and the effect of exogenous brn–3a to rescue the retinal defects associated with brn–3b–null mice was analyzed. Results: The exogenous brn–3a was expressed in a spatiotemporal manner identical to that of endogenous brn–3b and knock–in of brn–3a at brn–3b locus could functionally restore the development and survival of retinal ganglion cells (RGCs) in brn–3b–null mice. Furthermore, the expression of ectopic Brn–3a fully reinstates the expression of brn–3b–downsteam target genes in RGCs. Conclusions: These results indicate that the distinctive brn–3 temporospatial expression patterns dictate their unique roles in neurogenesis and suggest a conserved brn–3 regulatory pathway in the cell differentiation and survival shared by retinal and other sensory neurons.

Keywords: transcription factors • retinal development • genetics 
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