Rab23 regulates Nodal signaling in vertebrate left-right patterning independently of the Hedgehog pathway.
Asymmetric fluid flow in the node and Nodal signaling in the left lateral plate mesoderm (LPM) drive left-right patterning of the mammalian body plan. However, the mechanisms linking fluid flow to asymmetric gene expression in the LPM remain unclear. Here we show that the small GTPase Rab23, known for its role in Hedgehog signaling, plays a separate role in Nodal signaling and left-right patterning in the mouse embryo. Rab23 is not required for initial symmetry breaking in the node, but it is required for expression of Nodal and Nodal target genes in the LPM. Microinjection of Nodal protein and transfection of Nodal cDNA in the embryo indicate that Rab23 is required for the production of functional Nodal signals, rather than the response to them. Using gain- and loss-of function approaches, we show that Rab23 plays a similar role in zebrafish, where it is required in the teleost equivalent of the mouse node, Kupffer׳s vesicle. Collectively, these data suggest that Rab23 is an essential component of the mechanism that transmits asymmetric patterning information from the node to the LPM.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States.
Kimberly
K
Fuller
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States.
Joyce T
JT
O'Connell
Department of Genetics, University of Georgia, Athens, GA 30602, United States.
Julie
J
Gordon
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States.
Olivier
O
Mauti
Department of Genetics, University of Georgia, Athens, GA 30602, United States. Electronic address: jeggensc@uga.edu.
Jonathan
J
Eggenschwiler
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D046149:Embryo Culture Techniques; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D055452:Growth Differentiation Factor 1 / Q000096:biosynthesis / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism; D016547:Kinesins / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008648:Mesoderm / Q000196:embryology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D060172:Morpholinos / Q000235:genetics; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000075746:Zinc Finger Protein Gli2; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C000618551:Gli2 protein, mouse; D055452:Growth Differentiation Factor 1; D053823:Hedgehog Proteins; C490202:Kif3a protein, mouse; D051741:Kruppel-Like Transcription Factors; D060172:Morpholinos; D055457:Nodal Protein; C526008:Nodal protein, mouse; D029961:Zebrafish Proteins; D000075746:Zinc Finger Protein Gli2; C431746:Rab23 protein, mouse; C000590071:Rab23 protein, zebrafish; D016547:Kinesins; D020691:rab GTP-Binding Proteins
Hedgehog; Lateral plate mesoderm; Mouse; Nodal; Node; Rab23; Zebrafish