Pbx homeodomain proteins pattern both the zebrafish retina and tectum

Curtis R French,John Ngai,Cecilia B Moens,Jennifer Stout,Karyn M Berry,Daniel W Hagey,Andrew J Waskiewicz,Katrin Wuennenberg-Stapleton,Ron Koss,Davon Callander,Timothy Erickson

doi:10.1186/1471-213x-7-85

Abstract

BackgroundPbx genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood. Within the hindbrain, Pbx cooperates with Hox proteins to regulate rhombomere segment identity. Pbx cooperates with Eng to regulate midbrain-hindbrain boundary maintenance, and with MyoD to control fast muscle cell differentiation. Although previous results have demonstrated that Pbx is required for proper eye size, functions in regulating retinal cell identity and patterning have not yet been examined.ResultsAnalysis of retinal ganglion cell axon pathfinding and outgrowth in pbx2/4 null embryos demonstrated a key role for pbx genes in regulating neural cell behavior. To identify Pbx-dependent genes involved in regulating retino-tectal pathfinding, we conducted a microarray screen for Pbx-dependent transcripts in zebrafish, and detected genes that are specifically expressed in the eye and tectum. A subset of Pbx-dependent retinal transcripts delineate specific domains in the dorso-temporal lobe of the developing retina. Furthermore, we determined that some Pbx-dependent transcripts also require Meis1 and Gdf6a function. Since gdf6a expression is also dependent on Pbx, we propose a model in which Pbx proteins regulate expression of the growth factor gdf6a, which in turn regulates patterning of the dorso-temporal lobe of the retina. This, in concert with aberrant tectal patterning in pbx2/4 null embryos, may lead to the observed defects in RGC outgrowth.ConclusionThese data define a novel role for Pbx in patterning the vertebrate retina and tectum in a manner required for proper retinal ganglion cell axon outgrowth.

Highlights

Pbx genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood
Retinal laminar structure is normal but retinal ganglion cell axon outgrowth is aberrant in pbx2/4 null embryos Previous studies have demonstrated a clear role for the homeodomain transcription factor Pbx in regulating cell fates in the hindbrain and at the midbrain-hindbrain boundary
The laminar structure of the retina appears relatively normal in pbx2/4 null embryos and the optic nerve exits the eye in the correct location

Summary

Introduction

Pbx genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood. Using mouse knockout and zebrafish knockdown models, researchers have shown that Pbx proteins are required to specify cell fate in the midbrain, hindbrain, somites, pancreas, and blood [1,2,3,4]. Pbx – Meis complexes have been implicated in megakaryocyte differentiation in rats, through the ability to initiate transcription from the platelet factor 4 (PF4) promoter [4]. It has been shown during the development of skeletal muscle that Pbx is constitutively bound to the Myogenin promoter, can bind directly to the bHLH transcription factor MyoD, and is required for the development of muscle cell fates [7]. A zebrafish mutant, lazarus (lzr), that contains a null mutation in the pbx gene [8], displays global defects in embryonic patterning including hindbrain, muscle, blood, and midbrain tissues

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