期刊
DEVELOPMENTAL DYNAMICS
卷 237, 期 5, 页码 1359-1372出版社
WILEY
DOI: 10.1002/dvdy.21536
关键词
HH-independent ventral midbrain specification; midbrain-hindbrain boundary; size regulation; roof plate; oculomotor neurons; dopaminergic neurons; Evx1
资金
- NINDS NIH HHS [R01 NS049091-03, R01 NS049091] Funding Source: Medline
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 upregulated (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.
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