runx3, egr1 and sox9b form a regulatory cascade required to modulate bmp-signaling during cranial cartilage development in zebrafishrunx3,egr1 sox9b形成监管级联需要调节bmp信号在颅软骨斑马鱼的发展.pdfVIP

RUNX3, EGR1 and SOX9B Form a Regulatory Cascade Required to Modulate BMP-Signaling during Cranial Cartilage Development in Zebrafish 1 1¤ ´ 1 1 2 1 Julia Dalcq , Vincent Pasque , Aurelie Ghaye , Arnaud Larbuisson , Patrick Motte , Joseph A. Martial , Marc Muller1* ´ ` ` 1 Laboratory for Molecular Biology and Genetic Engineering, GIGA-R, Universite de Liege, Liege, Belgium, 2 Plant Functional Genomics and Molecular Imaging and Center ` ` for Assistance in Technology of Microscopy, University of Liege, Liege, Belgium Abstract The cartilaginous elements forming the pharyngeal arches of the zebrafish derive from cranial neural crest cells. Their proper differentiation and patterning are regulated by reciprocal interactions between neural crest cells and surrounding endodermal, ectodermal and mesodermal tissues. In this study, we show that the endodermal factors Runx3 and Sox9b form a regulatory cascade with Egr1 resulting in transcriptional repression of the fsta gene, encoding a BMP antagonist, in pharyngeal endoderm. Using a transgenic line expressing a dominant negative BMP receptor or a specific BMP inhibitor (dorsomorphin), we show that BMP signaling is indeed required around 30 hpf in the neural crest cells to allow cell differentiation and proper pharyngeal cartilage formation. Runx3, Egr1, Sox9b and BMP signaling are required for expression of runx2b, one of the key regulator of cranial cartilage maturation and bone formation. Finally, we show that egr1 depletion leads to increased express