title: Precocious retinal neurons: Pax6 controls timing of differentiation and determination of cell type.
abstract: The transcription factor Pax6 plays a pivotal role in eye development, as eye morphogenesis is arrested at a primitive optic vesicle stage in homozygous Pax6 mutant mouse embryos. The arrested optic vesicle development has led to the assumption that cellular differentiation programs are unable to initiate. Contrary to this, we found that neurogenesis in Pax6 mutant optic vesicles was not arrested, but instead accelerated as numerous neurons differentiated precociously, more than a day earlier than normal. To identify potential mechanisms for Pax6 repression of neuron differentiation, we examined retinal proliferation and differentiation. Mutant optic vesicles had reduced proliferation, coupled with precocious activation of the proneural gene, Mash1. Ectopic expression of Mash1 was sufficient to induce precocious neuron differentiation. Subsequently, precocious neurons adopted a generic rather than a specific retinal neuron fate. Thus, Pax6 regulates the timing of retinal neurogenesis and couples it with specific neuron differentiation programs.
authors.affiliation: Biology Department, University of Nevada, Biology/200, 1664 N. Virginia Street, Reno, NV 89557, USA.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Philips
authors.forename: Carrie N
authors.initials: CN
authors.lastname: Stair
authors.forename: Hae
authors.initials: H
authors.lastname: Young Lee
authors.forename: Emily
authors.initials: E
authors.lastname: Wroblewski
authors.forename: Michael A
authors.initials: MA
authors.lastname: Berberoglu
authors.forename: Nadean L
authors.initials: NL
authors.lastname: Brown
authors.forename: Grant S
authors.initials: GS
authors.lastname: Mastick
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004628:Embryonic Structures / Q000033:anatomy & histology / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000002:abnormalities / Q000166:cytology* / Q000254:growth & development*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C000605732:Pax6 protein, mouse
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