Lisa E. Kelly

Ocular forkhead transcription factors: seeing eye to eye

Forkhead transcription factors comprise a large family of proteins with diverse functions during development. Recently, there has been accumulating evidence that several members of this family of proteins play an important role in the development of the vertebrate retina. Here, we summarize the cumulative data which demonstrates the integral role that forkhead factors play in cell cycle control of retinal precursors, as well as in cell fate determination, during retinal development. The expression patterns for 14 retinal expressed forkhead transcription factors are presented with an emphasis on comparing the expression profiles across species. The functional data regarding forkhead gene products expressed within the retina are discussed. As presented, these data suggest that forkhead gene products contribute to the complex regulation of proliferation and differentiation of retinal precursors during vertebrate eye development.

xArx2: an aristaless homolog that regulates brain regionalization during development in Xenopus laevis.

The aristaless‐related gene, Arx, plays a fundamental role in patterning the brain in humans and mice. Arx mutants exhibit lissencephaly among other anomalies. We have cloned a Xenopus aristaless homolog that appears to define specific regions of the developing forebrain. xArx2 is transcribed in blastula through neurula stages, and comes to be restricted to the ventral and lateral telencephalon, lateral diencephalon, neural floor plate of the anterior spinal cord, and somites. In this respect, Arx2 expresses in regions similar to Arx with the exception of the somites. Overexpression enlarges the telencephalon, and interference by means of antisense morpholino‐mediated translation knockdown reduces growth of this area. Overexpression and inhibition studies demonstrate that misregulation of xArx2 imposes dire consequences upon patterns of differentiation not only in the forebrain where the gene normally expresses, but also in more caudal brain territories and derivatives as well. This suggests that evolutionary changes that expanded Arx‐expression from ventral to dorsal prosencephalon might be one of the determinants that marked development and expansion of the telencephalon. genesis 47:19–31, 2009.

Identification of retinal homeobox (rax) gene-dependent genes by a microarray approach: the DNA endoglycosylase neil3 is a major downstream component of the rax genetic pathway: microarray analysis of rax downstream genes

Background: The retinal homeobox (rx/rax) gene is a transcription factor expressed in the developing eye field that is necessary for normal eye development. rax is necessary for retinal specification and stem cell development. The genetic program of early retinal development, including rax expression, can be induced in naïve ectoderm by activation of insulin‐like growth factor (IGF) signaling. We have undertaken a microarray‐based approach to identify rax‐dependent IGF‐induced genes. Results: We identified 21 IGF‐induced genes that exhibit at least a two‐fold decrease in expression when rax expression is knocked down. Ten of these genes were expressed in the developing eye, eight were expressed in the ciliary marginal zone of the mature tadpole retina, and four could significantly rescue the rax knockdown phenotype. One of these, the nei endonuclease VIII‐like 3 (neil3) gene, rescued the rax knockdown phenotype to a remarkable degree. We found that neil3 is necessary for normal retinal lamination and retinal neuron differentiation. Conclusions: We have identified neil3 as a component of the rax genetic pathway necessary for normal retinal progenitor cell development. neil3 is involved in the base excision DNA repair pathway, suggesting that this pathway is essential for normal rax‐dependent progenitor cell development in the mature retina. Developmental Dynamics 247:1199–1210, 2018.