complex regulation of cyp26a1 creates a robust retinoic acid gradient in the zebrafish embryo复杂的监管cyp26a1创建一个健壮的视黄酸梯度在斑马鱼胚胎.pdfVIP

PLoS BIOLOGY Complex Regulation of cyp26a1 Creates a Robust Retinoic Acid Gradient in the Zebrafish Embryo 1 2,3 1,3,4 1,4* Richard J. White , Qing Nie , Arthur D. Lander , Thomas F. Schilling 1 Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, United States of America, 2 Department of Mathematics, University of California Irvine, Irvine, California, United States of America, 3 Center for Complex Biological Systems, University of California Irvine, Irvine, California, United States of America, 4 Developmental Biology Center, University of California Irvine, Irvine, California, United States of America Positional identities along the anterior–posterior axis of the vertebrate nervous system are assigned during gastrulation by multiple posteriorizing signals, including retinoic acid (RA), fibroblast growth factors (Fgfs), and Wnts. Experimental evidence has suggested that RA, which is produced in paraxial mesoderm posterior to the hindbrain by aldehyde dehydrogenase 1a2 (aldh1a2/raldh2), forms a posterior-to-anterior gradient across the hindbrain field, and provides the positional information that specifies the locations and fates of rhombomeres. Recently, alternative models have been proposed in which RA plays only a permissive role, signaling wherever it is not degraded. Here we use a combination of experimental and modeling tools to address the role of RA in providing long-range positional cues in the zebrafish hindbrain. Using cell transplantation and implantation of RA-coated beads into RA-deficient zebrafish embryos, we demonstrate that RA can direc