TY - JOUR
T1 - Optic cup and lens development requires Pax6 expression in the early optic vesicle during a narrow time window
AU - Canto-Soler, M. Valeria
AU - Adler, Ruben
N1 - Funding Information:
The authors are grateful to Constance Cepko, Katherine Yutzey, Kunio Yasuda, Makoto Mochii and Olof Sundin for kind gifts of cDNA constructs and antibodies. They also thank the anonymous reviewers for their thoughtful suggestions; James Summerton and Paul Morcos from GeneTools, LLC for their advice on morpholino technology; David Kays for development of technical instruments; members of the Adler lab for helpful discussions and Betty Bandell for secretarial assistance. This work was supported by NIH grants EYO4859 (RA), and Core Grant EY1765, a center grant from the Foundation Fighting Blindness (Baltimore, MD), an unrestricted departmental grant from Research to Prevent Blindness, Inc. (New York, NY) and the Knights Templar Eye Foundation, Inc. (Schaumburg, IL). RA is the Arnall Patz Distinguished Professor of Ophthalmology.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - Pax6 mutations cause complex ocular malformations, but it is uncertain whether early eye development normally requires Pax6 function in both the optic vesicle (OV) and the lens epithelium, or only in the latter. To investigate this question, we electroporated the OV with anti-Pax6 or control morpholinos before the onset of lens placode formation. Pax6 downregulation was already detectable in the OV 10 h after anti-Pax6 treatment, and was accompanied by a significant increase in the death of OV cells. A small eye-like phenotype developed thereafter, whose severity was developmental stage-dependent. When treatment was applied at Hamburger Hamilton (HH) stage 10, there was no optic cup formation, and lens development was abortive despite normal Pax6 expression in the lens epithelium. Treatment at HH stage 11 resulted in structurally normal lens and optic cup, although the latter showed abnormal expression domains for several transcription factors. Early eye development therefore requires cell-autonomous Pax6 function not only in the lens but also in the optic vesicle, where it plays a hitherto unknown role in cell survival. The results, moreover, indicate that there is a critical stage during which Pax6 expression in the OV is necessary for normal lens development.
AB - Pax6 mutations cause complex ocular malformations, but it is uncertain whether early eye development normally requires Pax6 function in both the optic vesicle (OV) and the lens epithelium, or only in the latter. To investigate this question, we electroporated the OV with anti-Pax6 or control morpholinos before the onset of lens placode formation. Pax6 downregulation was already detectable in the OV 10 h after anti-Pax6 treatment, and was accompanied by a significant increase in the death of OV cells. A small eye-like phenotype developed thereafter, whose severity was developmental stage-dependent. When treatment was applied at Hamburger Hamilton (HH) stage 10, there was no optic cup formation, and lens development was abortive despite normal Pax6 expression in the lens epithelium. Treatment at HH stage 11 resulted in structurally normal lens and optic cup, although the latter showed abnormal expression domains for several transcription factors. Early eye development therefore requires cell-autonomous Pax6 function not only in the lens but also in the optic vesicle, where it plays a hitherto unknown role in cell survival. The results, moreover, indicate that there is a critical stage during which Pax6 expression in the OV is necessary for normal lens development.
KW - Aniridia
KW - Cell death
KW - Loss-of-function
KW - Morpholino
KW - Pax6
KW - Retina
KW - Small eye
KW - Transcription factors
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U2 - 10.1016/j.ydbio.2006.02.033
DO - 10.1016/j.ydbio.2006.02.033
M3 - Article
C2 - 16564518
AN - SCOPUS:33745926821
SN - 0012-1606
VL - 294
SP - 119
EP - 132
JO - Developmental biology
JF - Developmental biology
IS - 1
ER -