Dlx2 homeobox gene transcriptional regulation of Trkb neurotrophin receptor expression during mouse retinal development.

Abstract:

:Dlx homeobox genes are first expressed in embryonic retina at E11.5. The Dlx1/Dlx2 null retina has a reduced ganglion cell layer (GCL), with loss of late-born differentiated retinal ganglion cells (RGCs) due to increased apoptosis. TrkB signaling is proposed to regulate the dynamics of RGC apoptosis throughout development. DLX2 expression markedly precedes the onset of TrkB expression in the GCL; TrkB co-expression with Dlx2 and RGC markers is well-established by E13.5. In the Dlx1/Dlx2 null retina, TrkB expression is significantly reduced by E16.5. We demonstrated that DLX2 binds to a specific region of the TrkB promoter in retinal neuroepithelium during embryogenesis. In vitro confirmation and the functional consequences of DLX2 binding to this TrkB regulatory region support TrkB as a Dlx2 transcriptional target. Furthermore, ectopic Dlx2 expression in retinal explants activates TrkB expression and Dlx2 knockdown in primary retinal cultures results in reduced TrkB expression. RGC differentiation and survival require the coordinated expression of transcription factors. This study establishes a direct transcriptional relationship between a homeodomain protein involved in RGC differentiation and a neurotrophin receptor implicated in RGC survival. Signaling mediated by TrkB may contribute to survival of late-born RGCs whose terminal differentiation is regulated by Dlx gene function.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

de Melo J,Zhou QP,Zhang Q,Zhang S,Fonseca M,Wigle JT,Eisenstat DD

doi

10.1093/nar/gkm1099

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

872-84

issue

3

eissn

0305-1048

issn

1362-4962

pii

gkm1099

journal_volume

36

pub_type

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