Conference Paper

Morphological variations in eye size: does rx3 play a role?

Sifuentes-Romero I. and Kowalko, J.E.

Record Number:
4295
Year:
2019
Abstract:
In vertebrates, eyes form from a single eye field, specified from the neural epithelium during gastrulation. Under the influence of multiple signaling factors, this field splits into two bilateral regions each containing the primordium of both retina and lens. During neurulation, the retina primordium evaginates laterally from the forebrain, giving rise to the optic vesicles, the first morphological eye features that form. Several transcription factors required for optic vesicle development have been identified; among them, the retinal homeobox transcription factor, RX (also known as retina and anterior neural fold homeobox, RAX) has an evolutionarily conserved role during early vertebrate eye development. Loss of function mutations in Rx/Rax in mammals or rx3 in fish, result in loss of optic vesicle evagination and a complete lack of eyes. Additionally, in humans RAX has been associated with structural eye defects such as anophthalmia (absence of eyes) or microphthalmia (small eyes), but the actual role that RAX plays in these morphological variations in eye size is still unknown. Astyanax mexicanus is a single species consisting of eyed surface-dwelling (surface fish) and blind cave-dwelling (cavefish) morphs. Surface fish develop large eyes while cavefish initiate eye development. However, developmental alterations in cavefish lead to differences in eye size and morphogenesis, and ultimately result in the degeneration of the eye. These distinct morphological differences that arise during development make Astyanax a powerful system for studying the genetic regulation of eye size. Furthermore, previous studies demonstrated that rx3 is located under a QTL for eye size in the Astyanax mexicanus cavefish, suggesting that this gene may play a role in the evolution of eye size reduction in cavefish. We conducted gene expression analyses to quantify levels of expression and determine the rx3 expression domain in embryos of surface fish and two independentlyevolved cavefish populations. Our data suggest that the rx3 expression domain is reduced in size early in Pachon cavefish development. Interestingly, this reduction in rx3 expression domain size was not as pronounced in Molino cavefish, suggesting that different molecular and developmental mechanisms underlie reduced eye size in these two cave populations. Further, we have recently used CRISPR/Cas9 gene-editing to generate surface fish with mutations in rx3. Injected surface fish have eyes that are greatly reduced in size or entirely absent compared to uninjected siblings, suggesting a conserved role for this gene in early eye development in Astyanax mexicanus. We are currently isolating rx3 mutant lines of fish to examine the role of regulation of expression of this gene in eye size. Together, these results will allow us to unravel the role that rx3 is playing during eye development and how differences in rx3 expression regulate differences in eye morphogenesis, critical to understanding the mechanisms that lead to different congenital eye disorders.
Times Cited:
1
Conference Name:
Astyanax Interrnational Meeting
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