TY - JOUR
T1 - A novel role of the hedgehog pathway in lens regeneration
AU - Tsonis, Panagiotis A.
AU - Vergara, M. Natalia
AU - Spence, Jason R.
AU - Madhavan, Mayur
AU - Kramer, Elizabeth L.
AU - Call, Mindy K.
AU - Santiago, William G.
AU - Vallance, Jefferson E.
AU - Robbins, David J.
AU - Del Rio-Tsonis, Katia
N1 - Funding Information:
This work was supported by NIH grant EY10540 to PAT. We would like to thank Dr. James Chen and Dr. Philip Beachy for providing KAAD, Dr. Andrew McMahon for providing the HIP constructs, Dr. J. P Brockes, Dr. K. Takeshima, and Dr. Y. Imokawa for providing the newt clones used to make in situ probes, Dr. Goro Eguchi for providing the crystallin antibody, and Dr. Hans-Georg Simon for providing newt embryos. We would also like to thank Dr. Paul James for helpful discussions and Dr. P.A. Kahn for providing newt embryo staging information.
PY - 2004/3/15
Y1 - 2004/3/15
N2 - Lens regeneration in the adult newt is a classic example of replacing a lost organ by the process of transdifferentiation. After lens removal, the pigmented epithelial cells of the dorsal iris proliferate and dedifferentiate to form a lens vesicle, which subsequently differentiates to form a new lens. In searching for factors that control this remarkable process, we investigated the expression and role of hedgehog pathway members. These molecules are known to affect retina and pigment epithelium morphogenesis and have been recently shown to be involved in repair processes. Here we show that Shh, Ihh, ptc-1, and ptc-2 are expressed during lens regeneration. The expression of Shh and Ihh is quite unique since these genes have never been detected in lens. Interestingly, both Shh and Ihh are only expressed in the regenerating and developing lens, but not in the intact lens. Interfering with the hedgehog pathway results in considerable inhibition of the process of lens regeneration, including decreased cell proliferation as well as interference with lens fiber differentiation in the regenerating lens vesicle. Down-regulation of ptc-1 was also observed when inhibiting the pathway. These results provide the first evidence of a novel role for the hedgehog pathway in specific regulation of the regenerating lens.
AB - Lens regeneration in the adult newt is a classic example of replacing a lost organ by the process of transdifferentiation. After lens removal, the pigmented epithelial cells of the dorsal iris proliferate and dedifferentiate to form a lens vesicle, which subsequently differentiates to form a new lens. In searching for factors that control this remarkable process, we investigated the expression and role of hedgehog pathway members. These molecules are known to affect retina and pigment epithelium morphogenesis and have been recently shown to be involved in repair processes. Here we show that Shh, Ihh, ptc-1, and ptc-2 are expressed during lens regeneration. The expression of Shh and Ihh is quite unique since these genes have never been detected in lens. Interestingly, both Shh and Ihh are only expressed in the regenerating and developing lens, but not in the intact lens. Interfering with the hedgehog pathway results in considerable inhibition of the process of lens regeneration, including decreased cell proliferation as well as interference with lens fiber differentiation in the regenerating lens vesicle. Down-regulation of ptc-1 was also observed when inhibiting the pathway. These results provide the first evidence of a novel role for the hedgehog pathway in specific regulation of the regenerating lens.
KW - HIP
KW - Ihh
KW - KAAD
KW - Lens
KW - Regeneration
KW - Shh
KW - Transdifferentiation
KW - ptc-1
KW - ptc-2
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U2 - 10.1016/j.ydbio.2003.12.005
DO - 10.1016/j.ydbio.2003.12.005
M3 - Article
C2 - 15013805
AN - SCOPUS:12144288186
SN - 0012-1606
VL - 267
SP - 450
EP - 461
JO - Developmental biology
JF - Developmental biology
IS - 2
ER -