Primary cilium and sonic hedgehog signaling during neural tube patterning: Role of GPCRs and second messengers

Kasturi Pal, Saikat Mukhopadhyay

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)337-348
Number of pages12
JournalDevelopmental Neurobiology
Volume75
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • G-protein-coupled receptor
  • Hedgehog
  • Neural tube
  • Primary cilium
  • Protein kinase A

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Primary cilium and sonic hedgehog signaling during neural tube patterning: Role of GPCRs and second messengers'. Together they form a unique fingerprint.

  • Cite this