title: Replacement of related POU transcription factors leads to severe defects in mouse forebrain development.
abstract: Related transcription factors of the POU protein family show extensive overlap of expression in vivo and exhibit very similar biochemical properties in vitro. To study functional equivalence of class III POU proteins in vivo, we exchanged the Oct-6 gene by Brn-1 in the mouse. Brn-1 can fully replace Oct-6 in Schwann cells and rescue peripheral nervous system development in these mice. The same mice, however, exhibit severe defects in forebrain development arguing that Oct-6 and Brn-1 are not functionally equivalent in the central nervous system. The cause of the observed forebrain phenotype is complex, but anteriorly expanded Wnt1 expression contributes. Oct-6 normally represses Wnt1 expression in the early diencephalon and replacement by Brn-1 as a weaker inhibitor is no longer sufficient to maintain the necessary level of repression in the mouse mutant. The extent of functional equivalence between related transcription factors is thus strongly dependent on the analyzed tissue.
authors.affiliation: Institut für Biochemie, Emil-Fischer-Zentrum Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.forename: Petra
authors.initials: P
authors.lastname: Lommes
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sock
authors.forename: Simone
authors.initials: S
authors.lastname: Reiprich
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Friedrich
authors.forename: Jana
authors.initials: J
authors.lastname: Kriesch
authors.forename: C Claus
authors.initials: CC
authors.lastname: Stolt
authors.forename: John R
authors.initials: JR
authors.lastname: Bermingham
authors.forename: Michael
authors.initials: M
authors.lastname: Wegner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D017403:In Situ Hybridization; D008636:Mesencephalon / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000502:physiology; D050816:Octamer Transcription Factor-6 / Q000235:genetics / Q000378:metabolism*; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D016548:Prosencephalon / Q000002:abnormalities / Q000196:embryology; D012249:Rhombencephalon / Q000196:embryology; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D050816:Octamer Transcription Factor-6; C074065:Pou3f3 protein, mouse