Model organisms inform the search for the genes and developmental pathology underlying malformations of the human hindbrain

Semin Pediatr Neurol. 2009 Sep;16(3):155-63. doi: 10.1016/j.spen.2009.06.003.

Abstract

Congenital malformations of the human hindbrain, including the cerebellum, are poorly understood largely because their recognition is a relatively recent advance for imaging diagnostics. Cerebellar malformations are the most obvious and best characterized hindbrain malformations due to their relative ease of viewing by magnetic resonance imaging and the recent identification of several causative genes (Millen et al. Curr Opin Neurobiol 18:12-19, 2008). Malformations of the pons and medulla have also been described both in isolation and in association with cerebellar malformations (Barkovich et al. Ann Neurol 62:625-639, 2007). Although little is understood regarding the specific developmental pathologies underlying hindbrain malformations in humans, much is known regarding the mechanisms and genes driving hindbrain development in vertebrate model organisms. Thus, studies in vertebrate models provide a developmental framework in which to categorize human hindbrain malformations and serve to provide information regarding disrupted developmental processes and candidate genes. Here, we survey the basic principles of vertebrate hindbrain development and integrate our current knowledge of human hindbrain malformations into this framework.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Diseases / genetics*
  • Central Nervous System / abnormalities
  • Central Nervous System / growth & development
  • Central Nervous System / pathology
  • Cerebellum / abnormalities
  • Cerebellum / growth & development
  • Cerebellum / pathology
  • Disease Models, Animal
  • Humans
  • Rhombencephalon / abnormalities*
  • Rhombencephalon / growth & development*