Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects

Mol Neurobiol. 2011 Feb;43(1):12-26. doi: 10.1007/s12035-010-8154-0. Epub 2010 Nov 27.


Meckel-Gruber syndrome (MKS) is a severe autosomal recessively inherited disorder characterized by developmental defects of the central nervous system that comprise neural tube defects that most commonly present as occipital encephalocele. MKS is considered to be the most common syndromic form of neural tube defect. MKS is genetically heterogeneous with six known disease genes: MKS1, MKS2/TMEM216, MKS3/TMEM67, RPGRIP1L, CEP290, and CC2D2A with the encoded proteins all implicated in the correct function of primary cilia. Primary cilia are microtubule-based organelles that project from the apical surface of most epithelial cell types. Recent progress has implicated the involvement of cilia in the Wnt and Shh signaling pathways and has led to an understanding of their role in normal mammalian neurodevelopment. The aim of this review is to provide an overview of the molecular genetics of the human disorder, and to assess recent insights into the etiology and molecular cell biology of severe ciliopathies from mammalian animal models of MKS.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Abnormalities, Multiple / physiopathology
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Cilia / pathology
  • Cilia / physiology*
  • Cilia / ultrastructure
  • Ciliary Motility Disorders / epidemiology
  • Ciliary Motility Disorders / genetics*
  • Ciliary Motility Disorders / pathology
  • Ciliary Motility Disorders / physiopathology*
  • Diagnosis, Differential
  • Disease Models, Animal
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • History of Medicine
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Biology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neural Tube Defects / epidemiology
  • Neural Tube Defects / genetics*
  • Neural Tube Defects / pathology
  • Neural Tube Defects / physiopathology*
  • Proteins / genetics
  • Proteins / metabolism
  • Signal Transduction / physiology
  • Syndrome


  • Adaptor Proteins, Signal Transducing
  • Antigens, Neoplasm
  • CC2D2A protein, human
  • Cep290 protein, human
  • Hedgehog Proteins
  • MKS1 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Proteins
  • RPGRIP1L protein, human
  • TMEM216 protein, human
  • TMEM67 protein, human