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Publication : Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling.

First Author  Fogel JL Year  2008
Journal  Dev Dyn Volume  237
Issue  5 Pages  1359-72
PubMed ID  18429041 Mgi Jnum  J:134674
Mgi Id  MGI:3789518 Doi  10.1002/dvdy.21536
Citation  Fogel JL, et al. (2008) Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling. Dev Dyn 237(5):1359-72
abstractText  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. (c) 2008 Wiley-Liss, Inc.
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