title: Brn-3b inhibits generation of amacrine cells by binding to and negatively regulating DLX1/2 in developing retina.
abstract: During retinogenesis, the basic helix-loop-helix proneural gene math5 (atoh7) initiates the generation of the first-born neurons, retinal ganglion cells (RGCs), by activating a network of RGC transcription factors, including Brn-3b (POU4F2). Herein, we show that the expression of DLX1 and DLX2 is significantly down-regulated in math5-null retina but is markedly increased in Brn-3b-null retina. Interestingly, Brn-3b interacts with DLX1 through its homeodomain, and this interaction represses DLX1 activity. Retrovirus-mediated mis-expression of DLX1 or DLX2 dramatically increases the number of amacrine/bipolar cells and concurrently reduces rod photoreceptors. Conversely, combined ectopic expression of Brn-3b with DLX1 or DLX2 promotes the production of RGCs and inhibits amacrine cell differentiation. Thus, DLX1/2 play an essential role in cell fate selection between amacrine and RGCs. Brn-3b suppresses the role of DLX1/2 through physical interaction and biases the competent precursors toward RGC fates.
authors.affiliation: Department of Ophthalmology, University of Rochester, NY 14642, USA.
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: D D
authors.initials: DD
authors.lastname: Eisenstat
authors.forename: S
authors.initials: S
authors.lastname: Chiba
authors.forename: Y
authors.initials: Y
authors.lastname: Ishizaki
authors.forename: L
authors.initials: L
authors.lastname: Gan
authors.forename: K
authors.initials: K
authors.lastname: Shibasaki
mesh_terms: D025042:Amacrine Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055879:Gene Knock-In Techniques; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D050820:Transcription Factor Brn-3B / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; C085559:Pou4f2 protein, mouse; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors