Similarities and differences among inner retinal neurons revealed by the expression of reporter transgenes controlled by Brn-3a, Brn-3b, and Brn-3c promotor sequences.
Brn-3a, Brn-3b, and Brn-3c are highly homologous POU-domain transcription factors that are expressed in subsets of retinal ganglion cells. From each of the mouse Brn-3 genes, a DNA segment ranging in size from 4.6 to 13.4 kb and located immediately upstream of the start site of translation was joined to a human placental alkaline phosphatase (AP) reporter cDNA. Following the introduction of each construct into the mouse germline, a total of 19 transgenic lines were obtained, of which 16 expressed the AP reporter in the retina. Unexpectedly, at least 14 of the 16 expressing lines showed AP activity in subsets of amacrine cells, and these subsets typically differed among mouse lines injected with the same construct. Transgene expression was also found in ganglion cells in four lines and bipolar cells in seven lines. In all cases AP activity was confined to cells in the inner nuclear layer and the ganglion cell layer. The expression of Brn-3 transgenes in multiple cell types in the inner retina is reminiscent of earlier experiments in which visual pigment transgenes were found to be expressed in multiple cell types in the outer retina. Taken together, these observations suggest that anatomically and/or functionally related retinal neurons contain partially overlapping transcriptional regulatory specificities.
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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Nathans
D000469:Alkaline Phosphatase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D017930:Genes, Reporter / Q000502:physiology; D006651:Histocytochemistry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000201:enzymology*; D012160:Retina / Q000201:enzymology*; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D019076:Transgenes / Q000502:physiology*
D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; C494190:POU4F2 protein, human; C494189:Pou4f1 protein, mouse; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors; D000469:Alkaline Phosphatase