Hypomorphic Smo mutant with inefficient ciliary enrichment disrupts the highest level of vertebrate Hedgehog response

Developmental biology

Alyssa Bushey Long^2,1¹  Johanna Ben-Ami^2,3,1²  Eduardo D. Gigante^1,2³ 

[1]Department of Human Genetics, Emory University, Atlanta, GA 30322, USA^2

[2]Emory College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA^3

[3]Neuroscience Graduate Program, Emory University, Atlanta, GA 30322, USA^1

关键词: Smoothened;    Sonic hedgehog signaling;    Primary cilia;    Mouse development;   

DOI  :  10.1016/j.ydbio.2018.03.019

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Smoothened (Smo) is the essential transducer of Sonic hedgehog (Shh) signaling, which regulates cell fate and proliferation during embryogenesis. We identified a novel mouse mutant, cabbie (cbb), and found that its cause is a missense mutation in Smo. We showed the Smocbb mutation is insensitive to the Shh agonist SAG, perhaps due to the disruption of SAG binding. We characterized Smocbb for defects in craniofacial and skeletal development, as well as neural tube patterning, and revealed Smocbb affected processes that require the highest levels of Shh activity. Smo is normally enriched in cilia upon Shh stimulation; however, we detected inefficient enrichment of Smo in Smocbb mutants whether we stimulated with Shh or SAG. Taken together, our data suggest that the highest levels of vertebrate Hedgehog signaling activity require efficient Smo ciliary enrichment.

【 授权许可】

CC BY