Oct4/Pou5f1 controls tissue-specific repressors in early zebrafish embryo

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JSRM/Vol6 No.2, 2010; p82

Proceedings of German Society for Stem Cell Research - 2010 (PGSSCR) (5th Annual Meeting)

Molecular Mechanisms-O32 Oct4/Pou5f1 controls tissue-specific repressors in early zebrafish embryo D. Onichtchouk1, F. Geier1, D.M. Messerschmidt1, R. Mössner1, V. Taylor1, J. Timmer1, W. Driever1

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University of Freiburg, Department of Biology I, Developmental Biology Unit, Freiburg, Germany

Published on 23 Oct 2010

The transcription factor Pou5f1/Oct4 controls pluripotency in mammalian ES cells, but little is known about its role in early development. pou5f1 homologues are ubiquitously expressed during the gastrulation stages in vertebrates, and loss of its function leads to early embryonic lethality. Mouse Oct4 rescues severe gastrulation and axial defects of zebrafish pou5f1 null mutant MZspg, suggesting the phylogenetic conservation of Pou5f1 functions. Using time-resolved transcriptome analysis of zebrafish MZspg mutant embryos we found, that multiple differentiation and patterning genes are prematurely expressed in MZspg embryos, while expression of soxB1 class genes and some transcriptional repressors is reduced or absent. Our findings demonstrate that Pou5f1 controls differentiation timing by direct activation of transcriptional repressor sets specifically expressed in each main embryonic tissues: mesendoderm (foxD3), klfs in nonneural ectoderm (klf2b), neuroectoderm (her3 and hesx1). Significant overlap between zebrafish and mammalian Pou5f1 targets together with the ability of mouse Oct4 to replace for zebrafish Pou5f1 function suggests that the mammalian stem cell network may have evolved from a basal situation similar to what is observed in teleosts. In support of this

idea, tissue specificity of klfs and foxD3 expression in fish, correctly predicts the tissue-specificity of differentiation upon the knockout of respective mammalian homologues in ES cells (ectoderm and mesendoderm). The analysis of Pou5f1 downstream tissue-specific subnetwork will be presented. We envision that the knowledge of molecular interactions downstream of Pou5f1 in experimentally amenable models will contribute to the effort of directing differentiation of pluripotent stem cells to defined cell fates.

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Copyright © Journal of Stem cells and Regenerative medicine. All rights reserved JSRM/006020700048/Oct23, 2010. JSRM/Vol6 No.2, 2010; p82

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