title: A Pou5f1/Oct4 dependent Klf2a, Klf2b, and Klf17 regulatory sub-network contributes to EVL and ectoderm development during zebrafish embryogenesis.
abstract: In mammalian ES cells, the transcription factors Klf4 and Klf2 contribute to maintenance of pluripotency and self-renewal and are regulated by Pou5f1/Oct4. In the early zebrafish embryo Pou5f1/Oct4 is necessary for expression of three Klf2/4 family members, klf2a, klf2b and klf17 (previously klf4b), similar to the regulation reported for mammalian ES cells. In this study, we analyzed blastula and gastrula stage Klf regulatory networks and their influence on zebrafish embryonic patterning. We show that Pou5f1 acts in combination with region-specific factors to activate klf2a, klf2b, and klf17 in the superficial cell layer of the embryo. In addition, Pou5f1 acts together with the BMP signaling pathway to activate and maintain expression of klf2a and klf2b in a ventral ectodermal domain. We used microarray expression profiles of klf2a, klf2b and klf17 knockdown and overexpression embryos to identify Klf target genes, which reveals that Klfs participate in specification of the extraembryonic enveloping layer (EVL). We discuss mechanistic implications of simultaneous activation of transcriptional targets by ubiquitous, like Pou5f1, and region-specific inducers, emerging as a common regulatory motif in early development.
authors.affiliation: Developmental Biology Unit, Institute of Biology I, Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Kotkamp
authors.affiliation: Developmental Biology Unit, Institute of Biology I, Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mössner
authors.affiliation: Developmental Biology Unit, Institute of Biology I, Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Allen
authors.affiliation: Developmental Biology Unit, Institute of Biology I, Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany; Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs-University, Freiburg, Germany. Electronic address: Onichtchouk@biologie.uni-freiburg.de.
authors.forename: Daria
authors.initials: D
authors.lastname: Onichtchouk
authors.affiliation: Developmental Biology Unit, Institute of Biology I, Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany; Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs-University, Freiburg, Germany. Electronic address: driever@biologie.uni-freiburg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Driever
mesh_terms: D000818:Animals; D036703:Blastula / Q000196:embryology* / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004475:Ectoderm / Q000196:embryology* / Q000378:metabolism; D053263:Gene Regulatory Networks; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C085437:Pou5f3 protein, zebrafish; D029961:Zebrafish Proteins
keywords: Blastula; Ectoderm; Enveloping layer; Gastrulation; Gene regulatory network; Germ layers; Krüppel-like factors; Oct4; Pou5f1; Transcriptional regulation; Zebrafish