A cascade of irx1a and irx2a controls shh expression during retinogenesis.
In animal retina, hedgehog expression drives waves of neurogenesis, but genetic programs that control its expression during retinal neurogenesis are poorly elucidated. We have previously reported that irx1a is required for propagation of the sonic hedgehog (shh) expression waves in developing zebrafish retina. Here, we found that irx2a is expressed in the developing retina and that knockdown of irx2a results in a retinal phenotype strikingly similar to that of irx1a morphants. The expression of irx2a in retina ganglion cells was shown to be irx1a- and ath5-dependent suggesting that irx1a and ath5 are transcriptional regulators of irx2a. Furthermore, irx2a expression could rescue impaired propagation of shh waves in irx1a morphants. Together, these observations suggest that Irx2 functions downstream of irx1a to control shh expression in the retina. We proposed a novel transcriptional cascade of ath5-irx1a-irx2a in the regulation of hedgehog waves during vertebrate retinal development.
Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, China.
Siu Wah
SW
Choy
Chi Wa
CW
Cheng
Sin Ting
ST
Lee
Vincent Wai Tsun
VW
Li
Michelle Nga Yu
MN
Hui
Chi-Chung
CC
Hui
Dong
D
Liu
Shuk Han
SH
Cheng
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C413414:atoh7 protein, zebrafish; C501593:irx1a protein, zebrafish