title: NeuroD factors regulate cell fate and neurite stratification in the developing retina.
abstract: Members of the basic helix-loop-helix (bHLH) family of transcription factors have been shown to control critical aspects of development in many tissues. To identify bHLH genes that might regulate specific aspects of retinal cell development, we investigated the expression of bHLH genes in single, developing mouse retinal cells, with particular emphasis on the NeuroD family. Two of these factors, NeuroD2 and NeuroD6/NEX, had not been previously reported as expressed in the retina. A series of loss- and gain-of-function experiments was performed, which suggested that NeuroD genes have both similarities and differences in their activities. Notably, misexpression of NeuroD genes can direct amacrine cell processes to two to three specific sublaminae in the inner plexiform layer. This effect is specific to cell type and NeuroD gene, as the AII amacrine cell type is refractory to the effects of NeuroD1 and NeuroD6, but uniquely sensitive to the effect of NeuroD2 on neurite targeting. Additionally, NeuroD2 is endogenously expressed in AII amacrine cells, among others, and loss of NeuroD2 function results in a partial loss of AII amacrine cells. The effects of misexpressing NeuroD genes on retinal cell fate determination also suggested shared and divergent functions. Remarkably, NeuroD2 misexpression induced ganglion cell production even after the normal developmental window of ganglion cell genesis. Together, these data suggest that members of the NeuroD family are important for neuronal cell type identity and may be involved in several cell type-specific aspects of retinal development, including fate determination, differentiation, morphological development, and circuit formation.
authors: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Timothy J
authors: TJ
authors: Cherry
authors: Sui
authors: S
authors: Wang
authors: Ingo
authors: I
authors: Bormuth
authors: Markus
authors: M
authors: Schwab
authors: James
authors: J
authors: Olson
authors: Constance L
authors: CL
authors: Cepko
references: Dev Biol. 2001 Jun 1;234(1):174-87
references: 11356028
references: PLoS Biol. 2004 Sep;2(9):E247
references: 15226823
references: Neuron. 2008 Apr 10;58(1):65-77
references: 18400164
references: Nature. 2011 Feb 10;470(7333):259-63
references: 21270798
references: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):16-22
references: 14603031
references: Science. 1995 May 12;268(5212):836-44
references: 7754368
references: Nat Genet. 1999 Jan;21(1):70-1
references: 9916792
references: J Comp Neurol. 2008 Apr 10;507(5):1795-810
references: 18260140
references: Development. 2006 Dec;133(24):4815-25
references: 17092954
references: Development. 2000 Jul;127(14):3021-30
references: 10862740
references: Development. 2002 Feb;129(4):831-42
references: 11861467
references: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9495-500
references: 19470466
references: Curr Opin Neurobiol. 1999 Feb;9(1):37-46
references: 10072376
references: Mol Cell Neurosci. 1996;8(4):221-41
references: 9000438
references: Nat Rev Neurosci. 2002 Jul;3(7):517-30
references: 12094208
references: Cell. 2009 Nov 25;139(5):969-82
references: 19945380
references: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20067-71
references: 19104055
references: Semin Cell Dev Biol. 2004 Feb;15(1):83-9
references: 15036211
references: J Comp Neurol. 2008 Jul 10;509(2):225-38
references: 18465787
references: Prog Retin Eye Res. 2001 May;20(3):351-84
references: 11286897
references: J Comp Neurol. 2007 Jun 20;502(6):1047-65
references: 17444492
references: Cell. 2002 Sep 6;110(5):649-60
references: 12230981
references: Genes Dev. 1999 Jul 1;13(13):1647-52
references: 10398678
references: Anat Rec. 1985 Jun;212(2):199-205
references: 3842042
references: Nature. 2008 Jan 24;451(7177):470-4
references: 18216855
references: Genesis. 2006 Dec;44(12):611-21
references: 17146780
references: J Neurosci. 2000 May 15;20(10):3714-24
references: 10804213
references: Development. 2001 Apr;128(8):1313-22
references: 11262232
references: Science. 2009 Oct 23;326(5952):575-8
references: 19900895
references: Development. 1999 Jan;126(1):23-36
references: 9834183
references: Nat Neurosci. 2009 Oct;12(10):1308-16
references: 19734895
references: Neuron. 2010 Apr 15;66(1):15-36
references: 20399726
references: Neuron. 2004 Jan 22;41(2):229-41
references: 14741104
references: Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13239-44
references: 8917575
references: Curr Opin Neurobiol. 2001 Aug;11(4):431-6
references: 11502388
references: Curr Biol. 2004 Jul 13;14(13):R497-500
references: 15242626
references: Neuron. 2004 Sep 16;43(6):779-93
references: 15363390
references: Development. 2007 Nov;134(21):3771-80
references: 17898002
references: Dev Biol. 1996 Nov 25;180(1):227-41
references: 8948587
references: PLoS One. 2008 Feb 13;3(2):e1588
references: 18270576
references: Neuron. 2009 Nov 25;64(4):484-97
references: 19945391
references: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2415-20
references: 18272492
references: Neuron. 2006 Mar 2;49(5):683-95
references: 16504944
references: Curr Opin Neurobiol. 2010 Feb;20(1):6-13
references: 20022236
references: Genome Biol. 2002;3(6):RESEARCH0030
references: 12093377