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The Eya1 phosphatase promotes Shh signaling during hindbrain development and oncogenesis

Adriana Eisner1, Maria F Pazyra-Murphy1, Ershela Durresi2

  • 1Departments of Cancer Biology and Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

Developmental Cell
|March 31, 2015
PubMed

Insights

Eya1, a phosphatase, acts with Six1 to regulate Sonic hedgehog (Shh) signaling. This pathway is crucial for hindbrain development and medulloblastoma growth, identifying Eya1 and Six1 as key regulators in both processes.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Research

Background:

  • Sonic hedgehog (Shh) signaling is vital for embryonic development and cancer, but its regulatory mechanisms, particularly phosphatases, are not fully understood.
  • Protein phosphorylation influences Shh signaling, yet the specific phosphatases involved remain largely uncharacterized.

Purpose of the Study:

  • To identify phosphatases that regulate the Sonic hedgehog (Shh) signaling pathway.
  • To elucidate the role of identified phosphatases in Shh-dependent development and oncogenesis.

Main Methods:

  • Conducted a small hairpin RNA (shRNA) screen of the phosphatome to identify novel regulators of Shh signaling.
  • Investigated the interaction and function of Eya1 and Six1 in regulating Gli transcriptional activators.
  • Assessed the role of Eya1 in Shh-dependent hindbrain development and medulloblastoma growth.

Main Results:

  • Identified Eya1 as a positive regulator of Shh signaling through an shRNA screen.
  • Demonstrated that catalytically active Eya1 cooperates with Six1 to enhance gene induction in response to Shh.
  • Showed that Eya1 and Six1 together regulate Gli transcriptional activators, impacting hindbrain development and medulloblastoma progression.

Conclusions:

  • Eya1 and Six1 are identified as critical components of the Shh transcriptional network.
  • Eya1 plays a crucial role in Shh-dependent hindbrain development and is implicated in medulloblastoma growth.
  • These findings highlight Eya1 as a potential therapeutic target in Shh-driven cancers and developmental disorders.

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