Genes that control the size of the cerebral cortex.

Study of the mechanisms that control growth of the cerebral cortex has largely followed by analogy from work in invertebrate systems such as fly and worm. However, the identification of several genes that cause human microcephaly has provided new avenues of investigation into the mechanisms that control cell identity during cerebral cortical development. In vivo studies suggest that many forms of microcephaly result from defects in the control of cell fate: precocious formation of neurons during early developmental stages produces deficiencies in progenitor cells at later stages of neurogenesis, resulting in an overall small cerebral cortex.

The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate.

The hyh (hydrocephalus with hop gait) mouse shows a markedly small cerebral cortex at birth and dies postnatally from progressive enlargement of the ventricular system. Here we show that the small hyh cortex reflects altered cell fate. Neural progenitor cells withdraw prematurely from the cell cycle, producing more early-born, deep-layer cerebral cortical neurons but depleting the cortical progenitor pool, such that late-born, upper-layer cortical neurons are underproduced, creating a small cortex.

Mapping of the mouse hyh gene to a YAC/BAC contig on proximal Chromosome 7.

Mice that are homozygous for the autosomal recessive hydrocephaly with hop gait (hyh) mutation on Chromosome (Chr) 7 have congenital hydrocephalus characterized by an interhemispheric cyst arising from the third ventricle and agenesis of the corpus callosum. Analysis of more than 500 backcross and intercross progeny maps the hyh locus to proximal Chr 7, approximately 13 cM centromeric to its originally reported map position. Analysis of recombinants at several MIT microsatellite markers localized the hyh locus between D7Mit75 and D7Mit56.