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

Jimmy de Melo, Guoyan Du, Mario Fonseca, Leigh Anne Gillespie, William J. Turk, John L R Rubenstein, David D. Eisenstat

Research output: Contribution to journalArticle

Abstract

Dlx homeobox genes, the vertebrate homologs of Distalless, 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.

Original languageEnglish (US)
Pages (from-to)311-322
Number of pages12
JournalDevelopment
Volume132
Issue number2
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Retinal Ganglion Cells
Amacrine Cells
Retina
Homeobox Genes
Ganglia
Vertebrates
Retinal Cone Photoreceptor Cells
Retinal Rod Photoreceptor Cells
Optic Nerve
Prosencephalon
Knockout Mice
Embryonic Development
Cell Differentiation
Extremities
Parturition
Apoptosis
Phenotype
Genes

Keywords

  • Apoptosis
  • BrdU birthdating
  • Brn3b
  • Chx10
  • Crx
  • D1x1
  • D1x2
  • Homeobox
  • Mouse
  • Ocular retardation
  • Retina

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

de Melo, J., Du, G., Fonseca, M., Gillespie, L. A., Turk, W. J., Rubenstein, J. L. R., & Eisenstat, D. D. (2005). Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina. Development, 132(2), 311-322. https://doi.org/10.1242/dev.01560

Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina. / de Melo, Jimmy; Du, Guoyan; Fonseca, Mario; Gillespie, Leigh Anne; Turk, William J.; Rubenstein, John L R; Eisenstat, David D.

In: Development, Vol. 132, No. 2, 01.2005, p. 311-322.

Research output: Contribution to journalArticle

de Melo, J, Du, G, Fonseca, M, Gillespie, LA, Turk, WJ, Rubenstein, JLR & Eisenstat, DD 2005, 'Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina', Development, vol. 132, no. 2, pp. 311-322. https://doi.org/10.1242/dev.01560
de Melo, Jimmy ; Du, Guoyan ; Fonseca, Mario ; Gillespie, Leigh Anne ; Turk, William J. ; Rubenstein, John L R ; Eisenstat, David D. / Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina. In: Development. 2005 ; Vol. 132, No. 2. pp. 311-322.
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