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First published online 16 December 2004
doi: 10.1242/dev.01560

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Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina

¹ Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada
² Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, R3A 1S1, Canada
³ Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, R3E 0V9, Canada
⁴ Department of Psychiatry, University of California, San Francisco, CA 94143, USA
⁵ Department of Ophthalmology, University of Manitoba, Winnipeg, Manitoba, R3E 0V9, Canada

^* Author for correspondence (e-mail: eisensta{at}cc.umanitoba.ca)

Accepted 3 November 2004

Dlx homeobox genes, the vertebrate homologs of Distal-less, play important roles in the development of the vertebrate forebrain, craniofacial structures and limbs. Members of the Dlx gene family are also expressed in retinal ganglion cells (RGC), amacrine and horizontal cells of the developing and postnatal retina. Expression begins at embryonic day 12.5 and is maintained until late embryogenesis for Dlx1, while Dlx2 expression extends to adulthood. We have assessed the retinal phenotype of the Dlx1/Dlx2 double knockout mouse, which dies at birth. The Dlx1/2 null retina displays a reduced ganglion cell layer (GCL), with loss of differentiated RGCs due to increased apoptosis, and corresponding thinning of the optic nerve. Ectopic expression of Crx, the cone and rod photoreceptor homeobox gene, in the GCL and neuroblastic layers of the mutants may signify altered cell fate of uncommitted RGC progenitors. However, amacrine and horizontal cell differentiation is relatively unaffected in the Dlx1/2 null retina. Herein, we propose a model whereby early-born RGCs are Dlx1 and Dlx2 independent, but Dlx function is necessary for terminal differentiation of late-born RGC progenitors.

Key words: Apoptosis, Brn3b, BrdU birthdating, Chx10, Crx, Dlx1, Dlx2, Homeobox, Mouse, Ocular retardation, Retina

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