G-protein-coupled receptor signaling and neural tube closure defects

Issei S. Shimada, Saikat Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Disruption of the normal mechanisms that mediate neural tube closure can result in neural tube defects (NTDs) with devastating consequences in affected patients. With the advent of next-generation sequencing, we are increasingly detecting mutations in multiple genes in NTD cases. However, our ability to determine which of these genes contribute to the malformation is limited by our understanding of the pathways controlling neural tube closure. G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in humans and have been historically favored as drug targets. Recent studies implicate several GPCRs and downstream signaling pathways in neural tube development and closure. In this review, we will discuss our current understanding of GPCR signaling pathways in pathogenesis of NTDs. Notable examples include the orphan primary cilia-localized GPCR, Gpr161 that regulates the basal suppression machinery of sonic hedgehog pathway by means of activation of cAMP-protein kinase A signaling in the neural tube, and protease-activated receptors that are activated by a local network of membrane-tethered proteases during neural tube closure involving the surface ectoderm. Understanding the role of these GPCR-regulated pathways in neural tube development and closure is essential toward identification of underlying genetic causes to prevent NTDs.

Original languageEnglish (US)
Pages (from-to)129-139
Number of pages11
JournalBirth Defects Research
Issue number2
StatePublished - Jan 30 2017


  • CAMP
  • G-protein-coupled receptor
  • Gpr161
  • Neural tube defect
  • Primary cilia
  • Protease-activated receptor
  • Protein kinase A
  • Sonic hedgehog

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis


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