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Science 297 (5584): 1180-1183

Copyright © 2002 by the American Association for the Advancement of Science

Tissue-Specific Regulation of Retinal and Pituitary Precursor Cell Proliferation

Xue Li,1 Valentina Perissi,1 Forrest Liu,1 David W. Rose,2 Michael G. Rosenfeld1*

Mammalian organogenesis requires the expansion of pluripotent precursor cells before the subsequent determination of specific cell types, but the tissue-specific molecular mechanisms that regulate the initial expansion of primordial cells remain poorly defined. We have genetically established that Six6 homeodomain factor, acting as a strong tissue-specific repressor, regulates early progenitor cell proliferation during mammalian retinogenesis and pituitary development. Six6, in association with Dach corepressors, regulates proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. These data reveal a molecular mechanism by which a tissue-specific transcriptional repressor-corepressor complex can provide an organ-specific strategy for physiological expansion of precursor populations.

1 Howard Hughes Medical Institute, Department of Molecular Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, Room 345, La Jolla, CA 92093-0648, USA.
2 Department of Endocrinology and Metabolism, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0673, USA.
*   To whom correspondence should be addressed. E-mail: mrosenfeld @ucsd.edu



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