Purchase this article with an account.
X.-J. Yang, X.-M. Yang, T. Hashimoto; Sonic Hedgehog (Shh) Influences Retinal Ganglion Cell Genesis Through Regulation of Basic-Helix-Loop-Helix (bHLH) Transcription Factors. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1296.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Shh is a signaling molecule that plays critical roles in cell fate specification and cell proliferation during embryogenesis. In the vertebrate retina, the first-born retinal ganglion cells (RGCs) express Shh. Previously, we have shown that RGC-derived Shh negatively regulates RGC production behind the neurogenic wave front in the developing chicken retina. The purpose of this study is to further examine the cellular mechanisms that mediate the influence of Shh on retinogenesis. The bHLH protein Hes1 (chicken homologue Hairy2) is a transcription repressor and a downstream effector of Notch-Delta signaling pathway, which also suppresses RGC differentiation. The vertebrate homologue of the fly Atonal gene is a proneural bHLH gene required for RGC fate specification. We have investigated how Shh signaling influences these bHLH transcription factors during the peak period of RGC production in the chicken retina.
Retroviral viral vectors were used to express Shh or Ath5 and to infect the chicken retina in vivo during early retinogenesis. Effects of perturbing Shh and Ath5 expression were analyzed by in situ hybridization, RT-PCR, immunocytochemistry and flow cytometry.
During early chicken retinal development, Shh signals stimulated Hairy2 expression and suppressed Ath5 expression. Ath5 elevation behind the neurogenic wave front resulted in a dramatic overproduction of RGCs and a mild increase of photoreceptor cells. However, misexpression of Ath5 ahead of the neurogenic wave front only caused sporadic induction of precocious neurogenesis. Furthermore, forced Ath5 expression led to decreased proliferation of retinal progenitor cells by reducing S phase reentry.
This PDF is available to Subscribers Only