repressor dimerization in the zebrafish somitogenesis clock抑制因子二聚在斑马鱼somitogenesis时钟.pdfVIP

Repressor Dimerization in the Zebrafish Somitogenesis Clock Olivier Cinquin1,2,3¤* 1 Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, London, United Kingdom, 2 Department of Anatomy and ´ Developmental Biology, University College London, London, United Kingdom, 3 Laboratoire TIMC-IMAG, Centre national de la recherche scientifique, Universite Joseph ´ ´ Fourier, Faculte de Medecine, La Tronche, France The oscillations of the somitogenesis clock are linked to the fundamental process of vertebrate embryo segmentation, yet little is known about their generation. In zebrafish, it has been proposed that Her proteins repress the transcription of their own mRNA. However, in its simplest form, this model is incompatible with the fact that morpholino knockdown of Her proteins can impair expression of their mRNA. Simple self-repression models also do not account for the spatiotemporal pattern of gene expression, with waves of gene expression shrinking as they propagate. Here we study computationally the networks generated by the wealth of dimerization possibilities amongst transcriptional repressors in the zebrafish somitogenesis clock. These networks can reproduce knockdown phenotypes, and strongly suggest the existence of a Her1–Her7 heterodimer, so far untested experimentally. The networks are the first reported to reproduce the spatiotemporal pattern of the zebrafish somitogenesis clock; they shed new light on the role of Her13.2, the only known link between the somitogenesis clock and positional information in the paraxial mesoderm. The networks can also account for perturbations of the clock by manip