Long-range sclerotome induction by sonic hedgehog: direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway.
A long-range signal encoded by the Sonic hedgehog (Shh) gene has been implicated as the ventral patterning influence from the notochord that induces sclerotome and represses dermomyotome in somite differentiation. Long-range effects of hedgehog (hh) signaling have been suggested to result either from local induction of a secondary diffusible signal or from the direct action of the highly diffusible carboxy-terminal product of HH autoproteolytic cleavage. Here we provide evidence that the long-range somite patterning effects of SHH are instead mediated by a direct action of the amino-terminal cleavage product. We also show that pharmacological manipulations to increase the activity of cyclic AMP-dependent protein kinase A can selectively antagonize the effects of the amino-terminal cleavage product. Our results support the operation of a single evolutionarily conserved signaling pathway for both local and direct long-range inductive actions of HH family members.
Fan
C M
CM
Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Porter
J A
JA
Chiang
C
C
Chang
D T
DT
Beachy
P A
PA
Tessier-Lavigne
M
M
D000818:Animals; D015415:Biomarkers; D001842:Bone and Bones / Q000196:embryology*; D002450:Cell Communication; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004627:Embryonic Induction; D053823:Hedgehog Proteins; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008934:Mitogens; D009132:Muscles / Q000196:embryology; D010446:Peptide Fragments / Q000502:physiology; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012272:Ribs / Q000196:embryology; D015398:Signal Transduction; D012867:Skin / Q000196:embryology; D013131:Spine / Q000196:embryology; D015534:Trans-Activators
D015415:Biomarkers; D053823:Hedgehog Proteins; D008934:Mitogens; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases