title: Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis.
abstract: We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0650, USA. naybro@umich. edu.
authors.forename: N L
authors.initials: NL
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Kanekar
authors.forename: M L
authors.initials: ML
authors.lastname: Vetter
authors.forename: P K
authors.initials: PK
authors.lastname: Tucker
authors.forename: D L
authors.initials: DL
authors.lastname: Gemza
authors.forename: T
authors.initials: T
authors.lastname: Glaser
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004330:Drosophila; D004625:Embryo, Nonmammalian / Q000502:physiology; D004627:Embryonic Induction; D005314:Embryonic and Fetal Development; D019143:Evolution, Molecular; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins; D012160:Retina / Q000166:cytology / Q000196:embryology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014981:Xenopus
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; C117638:Atoh7 protein, mouse; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse