Regulation of proliferation, cell fate specification and differentiation by the homeodomain proteins Prox1, Six3, and Chx10 in the developing retina.
The coordination of proliferation and cell fate specification is of particular importance in the developing central nervous system, because different classes of neurons are generated at different stages of development. As a consequence, if too many or too few multipotent progenitor cells exit the cell cycle during the early stages of development, then a predictable shift in the ratio of neuronal cell types would occur. Such a perturbation could prove devastating for normal neural function. In the past several years, we have made numerous advances toward understanding the roles of cell cycle proteins in the development of the retina, a specialized region of the central nervous system. More recently, researchers have identified and characterized a number of homeodomain transcription factors that regulate the proliferation of retinal progenitor cells and the specification of cell fate. In this review, I will present recent findings about the homeodomain protein Prox1 and compare them with studies of two other homeodomain proteins that are important regulators of retinal development, Chx10 and Six3. Together, the research on the genes that encode these three proteins raises several new questions about the mechanisms underlying the coordination of proliferation and cell fate specification in the developing central nervous system.
Dyer
Michael A
MA
Department of Developmental Neurobiology, Mail Stop 323, St. Jude Children's Research Hospital, 332 N Lauderdale, Memphis, Tennessee 38105, USA. michael.dyer@stjude.org
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D056741:Cyclin D; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D000882:Haplorhini; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011995:Recombination, Genetic / Q000502:physiology; D012160:Retina / Q000196:embryology / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000097607:Homeobox Protein SIX3; D000098551:Prospero-Related Homeobox 1 Protein
D018797:Cell Cycle Proteins; D056741:Cyclin D; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097607:Homeobox Protein SIX3; D000098551:Prospero-Related Homeobox 1 Protein; C493961:Cdkn1b protein, mouse; C493965:Cdkn1c protein, mouse; C088975:Vsx2 protein, mouse