Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an antagonist of sonic hedgehog signaling in the somite.
The dorsal-ventral polarity of the somite is controlled by antagonistic signals from the dorsal neural tube/surface ectoderm, mediated by WNTs, and from the ventral notochord, mediated by sonic hedgehog (SHH). Each factor can act over a distance greater than a somite diameter in vitro, suggesting they must limit each other's actions within their own patterning domains in vivo. We show here that the growth-arrest specific gene 1 (Gas1), which is expressed in the dorsal somite, is induced by WNTs and encodes a protein that can bind to SHH. Furthermore, ectopic expression of Gas1 in presomitic cells attenuates the response of these cells to SHH in vitro. Taken together, these data suggest that GAS1 functions to reduce the availability of active SHH within the dorsal somite.
Lee
C S
CS
Department of Embryology, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, MD 21210, USA.
Buttitta
L
L
Fan
C M
CM
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D019556:COS Cells; D018797:Cell Cycle Proteins; D002522:Chlorocebus aethiops; D004627:Embryonic Induction / Q000502:physiology; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D015723:Gene Library; D017930:Genes, Reporter; D053823:Hedgehog Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000502:physiology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000502:physiology*; D014162:Transfection; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D018797:Cell Cycle Proteins; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; C501180:Gas1 protein, mouse; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D011505:Protein-Tyrosine Kinases