Genetic evidence that Sil is required for the Sonic Hedgehog response pathway.
The Sil gene encodes a cytosolic protein required for mouse embryonic midline and left/right axial development. Based on the phenotype of Sil mutant embryos, we hypothesized that Sil may be required for the activity of Sonic Hedgehog (Shh), a secreted signaling molecule also critically important for the development of the embryonic axes and found mutated in multiple types of cancer. Here we tested the genetic interaction between Sil and the Shh pathway by generating and analyzing embryos carrying mutations in both Sil and Patched (Ptch), a Shh receptor that normally inhibits the signaling pathway in the absence of ligand and when mutated leads to constitutive activation of the pathway. We find that Sil(-/-) Ptch(-/-) embryos do not activate the Shh pathway and instead have a phenotype indistinguishable from Sil(-/-) embryos, in which there is a loss of activity of Shh. These results provide genetic evidence that Sil is an essential component of the Shh response, acting downstream to Ptch.
Izraeli
S
S
Lowe
L A
LA
Bertness
V L
VL
Campaner
S
S
Hahn
H
H
Kirsch
I R
IR
Kuehn
M R
MR
D000818:Animals; D016923:Cell Death / Q000235:genetics; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism*; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006257:Head / Q000196:embryology; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D015514:Oncogene Proteins, Fusion; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C103486:SIL protein, mouse; D015534:Trans-Activators