Control of somite patterning by Sonic hedgehog and its downstream signal response genes.
In the avian embryo, previous work has demonstrated that the notochord provides inductive signals to activate myoD and pax1 regulatory genes, which are expressed in the dorsal and ventral somite cells that give rise to myotomal and sclerotomal lineages. Here, we present bead implantation and antisense inhibition experiments that show that Sonic hedgehog is both a sufficient and essential notochord signal molecule for myoD and pax1 activation in somites. Furthermore, we show that genes of the Sonic hedgehog signal response pathway, specifically patched, the Sonic hedgehog receptor, and gli and gli2/4, zinc-finger transcription factors, are activated in coordination with somite formation, establishing that Sonic hedgehog response genes play a regulatory role in coordinating the response of somites to the constitutive notochord Sonic hedgehog signal. Furthermore, the expression of patched, gli and gli2/4 is differentially patterned in the somite, providing mechanisms for differentially transducing the Sonic hedgehog signal to the myotomal and sclerotomal lineages. Finally, we show that the activation of gli2/4 is controlled by the process of somite formation and signals from the surface ectoderm, whereas upregulation of patched and activation of gli is controlled by the process of somite formation and a Sonic hedgehog signal. The Sonic hedgehog signal response genes, therefore, have important functions in regulating the initiation of the Sonic hedgehog response in newly forming somites and in regulating the patterned expression of myoD and pax1 in the myotomal and sclerotomal lineages following somite formation.
Borycki
A G
AG
Department of Cell and Developmental Biology, Universityof Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.
Mendham
L
L
Emerson
C P
CP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D017570:MyoD Protein / Q000235:genetics / Q000502:physiology; D009672:Notochord / Q000196:embryology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology; D051761:Paired Box Transcription Factors; D000072079:Patched Receptors; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D011784:Quail / Q000196:embryology* / Q000235:genetics*; D011956:Receptors, Cell Surface; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D017570:MyoD Protein; D016376:Oligonucleotides, Antisense; D015513:Oncogene Proteins; D051761:Paired Box Transcription Factors; D000072079:Patched Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; C070835:PAX1 transcription factor