not really finished is crucial for development of the zebrafish outer retina and encodes a transcription factor highly homologous to human Nuclear Respiratory Factor-1 and avian Initiation Binding Repressor.
Not really finished (nrf), a larval-lethal mutation in zebrafish generated by retroviral insertion, causes specific retinal defects. Analysis of mutant retinae reveals an extensive loss of photoreceptors and their precursors around the onset of visual function. These neurons undergo apoptosis during differentiation, affecting all classes of photoreceptors, suggesting an essential function of nrf for the development of all types of photoreceptors. In the mutant, some photoreceptors escape cell death, are functional and, as judged by opsin expression, belong to at least three classes of cones and one class of rods. The protein encoded by nrf is a close homologue of human Nuclear Respiratory Factor 1 and avian Initiation Binding Repressor, transcriptional regulators binding the upstream consensus sequence RCGCRYGCGY. At 24 hours of development, prior to neuronal differentiation, nrf is expressed ubiquitously throughout the developing retina and central nervous system. At 48 hours of development, expression of nrf is detected in the ganglion cell layer, in the neurons of the inner nuclear layer, and in the optic nerve and optic tracts, and, at 72 hours of development, is no longer detectable by in situ hybridization. Mutants contain no detectable nrf mRNA and die within 2 weeks postfertilization as larvae with reduced brain size. On the basis of its similarity with NRF-1 and IBR, nrf is likely involved in transcriptional regulation of multiple target genes, including those that encode mitochondrial proteins, growth factor receptors and other transcription factors. This demonstrates the power of insertional mutagenesis as a means for characterizing novel genes necessary for vertebrate retinal development.
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. nhopkins@mit.edu
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Becker
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Burgess
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Amsterdam
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Allende
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Hopkins
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D030161:Avian Proteins; D002454:Cell Differentiation; D002490:Central Nervous System / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics; D005123:Eye / Q000196:embryology; D005136:Eye Proteins; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D051265:NF-E2-Related Factor 1; D009474:Neurons / Q000166:cytology; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D010786:Photoreceptor Cells / Q000196:embryology; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells; D017386:Sequence Homology, Amino Acid; D013477:Superior Colliculi / Q000196:embryology; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; C097075:IBR protein, Gallus gallus; D051265:NF-E2-Related Factor 1; C116462:NRF1 protein, zebrafish; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins