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Primary cilium and sonic hedgehog signaling during neural tube patterning: Role of GPCRs and second messengers
Author(s) -
Pal Kasturi,
Mukhopadhyay Saikat
Publication year - 2015
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22193
Subject(s) - cilium , biology , neural tube , microbiology and biotechnology , sonic hedgehog , gli3 , hedgehog signaling pathway , signal transduction , hedgehog , g protein coupled receptor , ciliogenesis , smoothened , transcription factor , repressor , genetics , embryo , gene
The ventral neural tube in vertebrates is patterned by a gradient of sonic hedgehog (Shh) secreted from the notochord and floor plate. Forward genetic screens first pointed to the role of the primary cilium in ventral neural tube patterning. Further research has shown that most components of the Shh pathway localize to or shuttle through the primary cilium. In the absence of Shh, the bifunctional Gli transcription factors are proteolytically processed into repressor forms in a protein kinase A (PKA)‐ and cilium‐dependent manner. Recent work suggests that the orphan G‐protein‐coupled receptor (GPCR) Gpr161 localizes to cilia, and functions as a negative regulator of Shh signaling by determining Gli processing via cAMP signaling. The primary cilium also functions as a signaling compartment for calcium in the Shh pathway. A better understanding of the role of the cilium as a signaling compartment, and the interplay of second messenger systems that regulate PKA activation and Gli amplification during signaling is critical for deciphering the role of Shh during development, neuronal differentiation, and tumorigenesis. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 337–348, 2015