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Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling
Author(s) -
Fogel Jennifer L.,
Chiang Chin,
Huang Xi,
Agarwala Seema
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21536
Subject(s) - midbrain , sonic hedgehog , smoothened , biology , hedgehog , hedgehog signaling pathway , gli3 , gli1 , microbiology and biotechnology , fgf8 , gli2 , signal transduction , anatomy , neuroscience , endocrinology , central nervous system , genetics , receptor , transcription factor , fibroblast growth factor , repressor , gene
Although Hedgehog (HH) signaling plays a critical role in patterning the ventral midbrain, its role in early midbrain specification is not known. We examined the midbrains of sonic hedgehog ( Shh ) and smoothened ( Smo ) mutant mice where HH signaling is respectively attenuated and eliminated. We show that some ventral ( Evx1+ ) cell fates are specified in the Shh −/− mouse in a Ptc1 ‐ and Gli1 ‐independent manner. HH‐independent ventral midbrain induction was further confirmed by the presence of a Pax7 ‐negative ventral midbrain territory in both Shh −/− and Smo −/− mice at and before embryonic day (E) 8.5. Midbrain signaling centers are severely disrupted in the Shh −/− mutant. Interestingly, dorsal markers are up‐regulated ( Wnt1 , Gdf7 , Pax7 ), down‐regulated ( Lfng ), or otherwise altered ( Zic1 ) in the Shh −/− midbrain. Together with the increased cell death seen specifically in Shh −/− dorsal midbrains (E8.5–E9), our results suggest specific regulation of dorsal patterning by SHH, rather than a simple deregulation due to its absence. Developmental Dynamics 237:1359‐1372, 2008. © 2008 Wiley‐Liss, Inc.