Research Projects

1997 - 1998

MOLECULAR MECHANISMS UNDERLYING THE MULTIPOTENCY OF DIFFERENTIATED PIGMENTED EPITHELIAL CELLS.

Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

Grant number
09680733
Japan Grant Number (JGN)
JP09680733
Grant amount
(Total)
3,300,000 Japanese Yen
(Direct funding)
3,300,000 Japanese Yen

Vertebrate pigmented epithelial cells (PECs) are unique in their ability to transdifferentiate to lens and neural retinal cells.To elucidate the molecular mechanisms underlying the multi-potency of PECs, we focused on the role and regulation of Mitf, a basic-helix-loop-helix-zipper transcriptional factor.
Chicken Mitf is first detected in the proximal region of the optic vesicle, a presumptive pigmented epithelium, at a stage when no other markers for PECs are detected.The expression increases according to the PEC differentiation both in vivo and in vitro.Mitf expression is down-regulated by FGF and EGF treatments, which induce dedifferentiation and transdifferentiation.Overexpression of Mitf using a retrovirus vector supports expression of pigment cell specific genes, mmpll5 and tyrosinase, and inhibits transdifferentiation
We found that a silver mutation in Japanese quail is caused by a loss-of-function mutation in the Mitf.A part of PECs in the silver quail spontaneously transdifferentiate to neural retinal cells in vivo.Isolated PECs from the silver mutant frequently transdifferentiate to both lens and neural cells in vitro with no addition of growth factors, while either FGF or EGF is required for wild type PECs to transdifferentiate.
These results demonstrate that Mitf has a critical role in regulation of transdifferentiation and suggest that the regulational mechanism for Mitf expression should be analysed to reveal the molecular mechanisms underlying the multi-potency OF pigmented epithelial cells.

Link information
KAKEN
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680733
ID information
  • Grant number : 09680733
  • Japan Grant Number (JGN) : JP09680733