What primary microcephaly can tell us about brain growth

Trends Mol Med. 2006 Aug;12(8):358-66. doi: 10.1016/j.molmed.2006.06.006. Epub 2006 Jul 10.

Abstract

Autosomal recessive primary microcephaly (MCPH) is a neuro-developmental disorder that causes a great reduction in brain growth in utero. MCPH is hypothesized to be a primary disorder of neurogenic mitosis, leading to reduced neuron number. Hence, MCPH proteins are likely to be important components of cellular pathways regulating human brain size. At least six genes can cause this disorder and four of these have recently been identified: autosomal recessive primary microcephaly 1 (MCPH1), abnormal spindle-like, microcephaly associated (ASPM), cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) and centromere protein J (CENPJ). Whereas aberration of ASPM is the most common cause of MCPH, MCPH1 patients can be more readily diagnosed by the finding of increased numbers of "prophase-like cells" on routine cytogenetic investigation. Three MCPH proteins are centrosomal components but have apparently diverse roles that affect mitosis. There is accumulating evidence that evolutionary changes to the MCPH genes have contributed to the large brain size seen in primates, particularly humans. The aim of this article is to review what has been learnt about the rare condition primary microcephaly and the information this provides about normal brain growth.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / growth & development*
  • Brain / metabolism
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Genes, Recessive / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology
  • Microcephaly / genetics
  • Microcephaly / physiopathology*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology
  • Models, Biological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology

Substances

  • CDK5RAP2 protein, human
  • CENPJ protein, human
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • MCPH1 protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins