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Immunostaining to Visualize Murine Enteric Nervous System Development
07:54

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Published on: April 29, 2015

L1cam acts as a modifier gene during enteric nervous system development.

Adam S Wallace1, Claudia Schmidt, Melitta Schachner

  • 1Department of Anatomy and Cell Biology, University of Melbourne, 3010, Australia.

Neurobiology of Disease
|August 11, 2010
PubMed
Summary

L1cam interacts with Sox10, a gene linked to Hirschsprung's disease (HSCR), to disrupt neural crest cell migration and increase aganglionosis incidence. This finding highlights L1cam's role as a modifier gene in HSCR etiology.

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Area of Science:

  • Developmental biology
  • Genetics
  • Neuroscience

Background:

  • Hirschsprung's disease (HSCR) results from incomplete colonization of the gut by neural crest cells.
  • Variability in HSCR suggests involvement of modifier genes.
  • Previous studies indicated a potential interaction between L1CAM and RET in HSCR patients.

Purpose of the Study:

  • To investigate the interaction between L1cam and genes associated with Hirschsprung's disease, specifically Ret, Gdnf, and Sox10.
  • To determine if L1cam acts as a modifier gene in the context of HSCR.

Main Methods:

  • Utilized a two-locus complementation approach in a mouse model.
  • Assessed the impact of combined genetic alterations on neural crest cell migration and gut colonization.
  • Analyzed gene expression and cell death in developing neural crest cells.

Main Results:

  • Loss of L1cam combined with heterozygous loss of Ret or Gdnf did not cause aganglionosis.
  • L1cam's interaction with Sox10 significantly increased the incidence of aganglionosis.
  • This interaction perturbed neural crest migration and led to excessive cell death before gut entry.
  • Sox10 was found to regulate L1cam expression.

Conclusions:

  • L1cam functions as a modifier gene for Sox10 in the context of Hirschsprung's disease.
  • The interaction between L1cam and Sox10 significantly contributes to the etiology of HSCR by affecting neural crest cell development and migration.