distinct roles of hand2 in initiating polarity and posterior shh expression during the onset of mouse limb bud development不同的角色hand2启动极性和后嘘表达在鼠标肢芽的发生发展.pdfVIP

Distinct Roles of Hand2 in Initiating Polarity and Posterior Shh Expression during the Onset of Mouse Limb Bud Development 1¤a 1 1 2 ´ 1 Antonella Galli * , Dimitri Robay , Marco Osterwalder , Xiaozhong Bao , Jean-Denis Benazet , 3¤b 3,4 2 1 Muhammad Tariq , Renato Paro , Susan Mackem , Rolf Zeller * 1 Developmental Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland, 2 Cancer and Developmental Biology Laboratory, National Cancer Institute, Bethesda, Maryland, United States of America, 3 Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland, 4 Faculty of Sciences, University of Basel, Basel, Switzerland Abstract The polarization of nascent embryonic fields and the endowment of cells with organizer properties are key to initiation of vertebrate organogenesis. One such event is antero-posterior (AP) polarization of early limb buds and activation of morphogenetic Sonic Hedgehog (SHH) signaling in the posterior mesenchyme, which in turn promotes outgrowth and specifies the pentadactylous autopod. Inactivation of the Hand2 transcriptional regulator from the onset of mouse forelimb bud development disrupts establishment of posterior identity and Shh expression, which results in a skeletal phenotype identical to Shh deficient limb buds. In wild-type limb buds, Hand2 is part of the protein complexes containing Hoxd13, another essential regulator of Shh activation in limb buds. Chromatin immunoprecipitation shows that Hand2-containing chromatin complexes are bound to the far upstream cis-regulatory region (ZRS), which i