The Genetic Sequence of Retinal Development in the Ciliary Margin of theXenopusEye

Abstract

The ciliary marginal zone is a perpetually self-renewing proliferative neuroepithelium at the perimeter of the retina in amphibians and fish. In the ciliary marginal zone (CMZ), cells are spatially ordered with respect to cellular development, deep stem cells being most peripheral and differentiating retinal progenitors being most central. This spatial gradient in the CMZ recapitulates embryonic retinogenesis and provides a powerful system to examine the relative order of gene expression during this process. A number of neurogenic and proneural genes have been described to have interacting roles in the development of the vertebrate nervous system, and so it is of major importance to put these genes in a hierarchical pathway. In no other system yet described are the developmental stages of neurogenesis arrayed so clearly in a spatial pattern as in the CMZ. We have therefore taken advantage of this system, using double in situ hybridizations on cross sections of the CMZ, to compare the spatial patterns of 15 proneural, neurogenic, and other genes involved in early and late phases of retinal development. In addition, we have positioned these expression patterns with respect to cell division. What emerges from this work is a spatial ordering of gene expression that predicts a genetic hierarchy governing vertebrate retinogenesis. By injecting messenger RNA for some of these genes into blastomeres of the Xenopus embryo and examining the effects on expression of the putative downstream genes, we have been able to corroborate some of the relationships between genes predicted to act sequentially.

Neurogenesis in the Fish Retina

“…Genes involved in regulating retinal neurogenesis, such as rx and pax6, are also expressed in the CGZ (Chuang et al, 1999;Hitchcock et al, 1996). Comparative expression patterns have been described for a number of these genes in the CGZ of the growing Xenopus retina, where the temporal sequence of expression-implied by differential distance from the iris epithelium-recapitulates the sequence of gene expression during embryonic retinal neurogenesis (Perron et al, 1998). Although this comparative expression experiment has not been performed using a teleost fish model, many of the same genes have been evaluated independently and are found in the CGZ.…”

Fibroblast growth factor–hedgehog interdependence during retina regeneration

“…As the eye develops, the CB and the CMZ become well defined so that the CB is composed of a two-layered epithelium, the pigmented epithelium (PE) and nonpigmented epithelium (NPE). The CMZ becomes a transitional zone between the peripheral retina and the CB (Perron et al, 1998;Reh, 2000, 2003). Only amphibians, fish, and birds house progenitor cells in the CMZ that are able to proliferate and add new neurons to the retina postnatally (reviewed in Haynes and Del Rio-Tsonis, 2004;Hitchcock et al, 2004).…”

Zebrafish dou yan mutation causes patterning defects and extensive cell death in the retina

“…Q-T: Interplexiform layer cells (IPC, red) are present in wild-type retinas (Q,R) but not in the mutant retina (S,T) at 78 hpf. Scale bars ϭ 20 m. tion factors that are required for early specification and morphogenesis of the eye, such as Pax6, Six3, Rx1, Lhx2, Tll, and Optx2, can lead to early onset of eyeless or small eye phenotypes that appear before retinal neurogenesis begins (Hill et al, 1991;Perron et al, 1998;Zuber et al, 2003). On the other hand, defects in genes that are required for the survival of differentiated retinal cells would be predicted to interfere with retinal growth and may even cause shrinkage of the eye.…”