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Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix

Rebecca G Norcross1, Lina Abdelmoti1, Eric C Rouchka2

  • 1Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, 40536, USA.

Developmental Biology
|October 20, 2022
PubMed

Insights

The scaffold protein Shoc2 is vital for embryonic development, particularly for neural crest (NC) cells. Loss of Shoc2 disrupts NC development and extracellular matrix (ECM) regulation, potentially causing Noonan-like syndrome with loose anagen hair (NSLH).

Area of Science:

  • Developmental Biology
  • Molecular Signaling

Background:

  • The extracellular signal-regulated kinase (ERK1/2) pathway is crucial for embryonic development.
  • The scaffold protein Shoc2 modulates ERK1/2 signaling and is implicated in Noonan-like syndrome with loose anagen hair (NSLH).
  • Shoc2 dysfunction impacts neural crest (NC) cell development.

Purpose of the Study:

  • To investigate the role of Shoc2-ERK1/2 signaling in zebrafish neural crest (NC) development.
  • To understand the molecular mechanisms underlying Shoc2's function in NC cell specification and differentiation.

Main Methods:

  • Utilized the zebrafish model system.
  • Generated shoc2 CRISPR/Cas9 mutant larvae.
  • Performed comparative transcriptome analysis on NC-derived cells.

Main Results:

  • Loss of Shoc2 significantly altered transcription factor expression regulating NC cell specification and differentiation.
  • Shoc2-mediated signaling regulates gene programs involved in extracellular matrix (ECM) protein synthesis and ECM regulation.
  • Transcriptome analysis revealed dysregulation of ECM-related genes in shoc2 mutants.

Conclusions:

  • Shoc2 is an essential regulator of neural crest (NC) development.
  • Imbalances in extracellular matrix (ECM) turnover may contribute to the developmental abnormalities observed in Noonan-like syndrome with loose anagen hair (NSLH).
  • Shoc2 plays a critical role in maintaining NC cell integrity through ECM regulation.
Keywords:
ERK1/2Neural crestNoonan-like syndrome with loose anagen hair (NSLH)Shoc2Zebrafish

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