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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

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Basal Suppression of the Sonic Hedgehog Pathway by the G-Protein-Coupled Receptor Gpr161 Restricts Medulloblastoma

Issei S Shimada1, Sun-Hee Hwang1, Bandarigoda N Somatilaka1

  • 1Department of Cell Biology , University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Cell Reports
|February 2, 2018
PubMed

Insights

Gpr161 acts as a tumor suppressor in medulloblastoma by controlling Sonic hedgehog (Shh) pathway activity. Its deletion promotes cerebellar granule cell progenitor proliferation, increasing tumor risk and severity.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cancer Research

Background:

  • Sonic hedgehog (Shh) signaling is crucial for cerebellar granule cell (GC) progenitor proliferation and medulloblastoma development.
  • The role of pathways regulating GC progenitors before Shh production and their involvement in tumorigenesis is not fully understood.
  • Gpr161, a cilium-localized receptor, is known to suppress Shh signaling in the neural tube.

Purpose of the Study:

  • To investigate the role of Gpr161 in regulating GC progenitor proliferation during embryogenesis.
  • To determine the function of Gpr161 in Shh-subtype medulloblastoma pathogenesis.
  • To elucidate the mechanisms by which Gpr161 influences Shh pathway activity and GC progenitor development.

Main Methods:

  • Conditional deletion of Gpr161 in mouse neural stem cells and GC progenitors.
  • Analysis of Shh pathway activity, GC progenitor generation, and proliferation.
  • Assessment of medulloblastoma incidence and severity following Gpr161 deletion.
  • Correlation of GPR161 expression with patient survival data.

Main Results:

  • Gpr161 deletion led to increased Shh pathway activity and enhanced GC progenitor proliferation, independent of Shh production.
  • Earlier deletion of Gpr161 during embryogenesis resulted in higher tumor incidence and severity.
  • GC progenitor overproduction due to Gpr161 deletion was dependent on cilia.
  • Low GPR161 expression in patients correlated with poorer survival in Shh-subtype medulloblastoma.

Conclusions:

  • Gpr161 functions as a tumor suppressor in Shh-subtype medulloblastoma.
  • Gpr161 restricts GC progenitor production by inhibiting premature and Shh-dependent pathway activation.
  • Basal suppression of the Shh pathway by Gpr161 is critical for preventing medulloblastoma development.
Keywords:
G-protein-coupled receptorGpr161cerebellumgranule cellmedulloblastomaprimary ciliasonic hedgehogtumor suppressor

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