Precocious retinal neurons: Pax6 controls timing of differentiation and determination of cell type.
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.
Philips
Gary T
GT
Biology Department, University of Nevada, Biology/200, 1664 N. Virginia Street, Reno, NV 89557, USA.
Stair
Carrie N
CN
Young Lee
Hae
H
Wroblewski
Emily
E
Berberoglu
Michael A
MA
Brown
Nadean L
NL
Mastick
Grant S
GS
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
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
Science. 1995 Mar 24;267(5205):1788-92
7892602
Development. 1995 May;121(5):1433-42
7789273
Development. 2002 Oct;129(19):4535-45
12223410
J Embryol Exp Morphol. 1986 Sep;97:95-110
3794606
Development. 1991 Dec;113(4):1435-49
1687460
Science. 1995 Nov 24;270(5240):1363-6
7481825
Anat Rec. 1985 Jun;212(2):199-205
3842042
Mech Dev. 1995 Nov;53(3):291-304
8645597
Biochem Biophys Res Commun. 1997 Jan 13;230(2):376-80
9016787
Curr Opin Neurobiol. 1999 Feb;9(1):37-46
10072376
Dev Biol. 2001 May 1;233(1):13-21
11319854
Development. 2001 Oct;128(20):3987-94
11641222
Brain Res Mol Brain Res. 1989 Mar;5(2):93-108
2469928
Development. 1999 Jan;126(1):23-36
9834183
Mol Cell Neurosci. 2003 May;23 (1):107-20
12799141
Nat Genet. 1994 Aug;7(4):463-71
7951315
Neuron. 2003 Oct 9;40(2):199-208
14556704
J Comp Neurol. 1996 May 27;369(2):319-27
8727003
Genesis. 2000 Nov-Dec;28(3-4):135-42
11105055
Development. 1992 Mar;114(3):643-51
1352238
Cell. 2001 Apr 6;105(1):43-55
11301001
Dev Biol. 1996 Jan 10;173(1):79-94
8575640
Development. 2002 May;129(10):2435-46
11973275
Science. 1988 Mar 4;239(4844):1142-5
2449732
Development. 2002 Jan;129(2):455-66
11807037
Genes Dev. 1995 Dec 15;9(24):3136-48
8543157
Genes Cells. 1996 Aug;1(8):765-74
9077445
Neuron. 1998 Nov;21(5):1031-44
9856459
Neuron. 1997 Nov;19(5):981-94
9390513
Nat Genet. 1992 Nov;2(3):232-9
1345175
Mech Dev. 1999 Jun;84(1-2):31-40
10473118
Development. 2003 Jul;130(14 ):3269-81
12783797
Development. 2000 Aug;127(15):3237-47
10887080
Genes Dev. 1990 Aug;4(8):1267-76
1977659
Nature. 1991 Dec 19-26;354(6354):522-5
1684639
Neuron. 1995 Jan;14(1):117-24
7826629
J Neurosci. 1993 Jan;13(1):285-99
8423474
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1649-54
11172005
Development. 1997 May;124(10 ):1985-97
9169845
Development. 2001 Jul;128(13):2497-508
11493566
Development. 2002 Nov;129(21):5029-40
12397111
J Neurobiol. 1996 Mar;29(3):399-413
8907167
Neuron. 1988 Mar;1(1):15-26
3272153
Semin Cell Dev Biol. 2001 Dec;12(6):491-8
11735385
Development. 2003 Jul;130(13):2903-15
12756174
Genes Dev. 2001 Jan 1;15(1):24-9
11156601
J Neurosci. 1987 Apr;7(4):1250-63
3553447
Development. 2001 Jan;128(2):193-205
11124115
Development. 1999 Feb;126(3):443-56
9876174
J Neurosci. 2002 Jun 1;22(11):4249-63
12040030
Development. 1998 Dec;125(23 ):4821-33
9806930
J Comp Neurol. 2003 Jun 23;461(2):187-204
12724837
Development. 1999 Oct;126(19):4213-22
10477290
Neuron. 1990 Jun;4(6):833-45
2163263
Neuron. 1996 Apr;16(4):723-34
8607991
Development. 1997 Mar;124(6):1119-31
9102299
Neuron. 1993 Oct;11(4):689-701
7691107
Development. 2002 Feb;129(4):831-42
11861467
Development. 1997 Apr;124(8):1573-82
9108373
J Neurosci. 1997 Oct 15;17(20):7831-8
9315903
Curr Opin Genet Dev. 1997 Oct;7(5):659-65
9388783
Mol Cell Neurosci. 2001 Jan;17 (1):190-207
11161479
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3920-5
8632990
Dev Dyn. 1992 Dec;195(4):231-72
1304821
Cell. 1995 Jun 2;81(5):747-56
7774016
Cereb Cortex. 1999 Sep;9(6):627-35
10498281
Brain Res. 1985 Jun;352(2):286-90
3896407
Development. 2003 Jan;130(1):111-21
12441296
Mech Dev. 1993 Aug;42(3):171-85
8217843
J Comp Neurol. 2004 Jun 21;474(2):304-24
15164429
Genetics. 2001 Dec;159(4):1689-700
11779807
Science. 1994 Aug 5;265(5173):785-9
7914031