Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog
J. Clin. Invest. Maisa Seppala, et al. 117:1575 doi:10.1172/JCI32032 [
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Figure 2Shh pathway gene expression in the craniofacial region of WT and
Gas1–/– mice.
(
A,
B,
F, and
G) At E10.5 and E11.5, sagittal sections demarcated
Shh in the pharyngeal endoderm, diencephalon, and facial ectoderm of WT embryos. (
C,
D,
H, and
I)
Ptc1 and
Gli1 demonstrated a gradient of transcriptional activity across these regions in response to signaling. (
E and
J) In contrast,
Gas1 was expressed at a distance from the source of
Shh transcription, in a partially overlapping domain with
Ptc1 and
Gli1, at their peripheral margins. (
K–
R) In
Gas1–/– embryos at both E10.5 and E11.5, there was a marked reduction in the domain of both
Ptc1 (
M and
Q) and
Gli1 (
N and
R) expression within the frontonasal (black arrows) and mandibular processes (blue arrows) compared with that of WT embryos (compare with respective arrows in
C,
D,
H, and
I), while
Shh expression was normal in
Gas1–/– compared with WT embryos (
B and
G) at both stages. di, diencephalon; fe, facial ectoderm; fnp, frontonasal process; md, mandibular process; ne, neural ectoderm; pe, pharyngeal endoderm; rp, Rathke’s pouch; t, telencephalon. Scale bar: 200 μm.
