Tissue-specific regulation of retinal and pituitary precursor cell proliferation.
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.
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.
Xue
X
Li
Valentina
V
Perissi
Forrest
F
Liu
David W
DW
Rose
Michael G
MG
Rosenfeld
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000166:cytology; D005136:Eye Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D010902:Pituitary Gland / Q000166:cytology* / Q000196:embryology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000196:embryology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; C486747:DACH1 protein, human; D004268:DNA-Binding Proteins; C456264:Dach1 protein, mouse; C485735:Dach2 protein, mouse; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C491945:SIX6 protein, human; C114419:Six6 protein, mouse; C486157:Skil protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases