Inactivation ofArx, the Murine Ortholog of the X-Linked Lissencephaly with Ambiguous Genitalia Gene, Leads to Severe Disorganization of the Ventral Telencephalon with Impaired Neuronal Migration and Differentiation

• DOI: 10.1523/jneurosci.0417-07.2007
• Publication Date: 2007-04-25T16:38:41Z
• Authors: Elena Colombo; Patrick Collombat; Gaia Colasante; Marta Bianchi; Jason Long; Ahmed Mansouri; John L. R. Rubens...; Vania Broccoli
• Keywords: Ganglionic eminence

ARX loss-of-function mutations cause X-linked lissencephaly with ambiguous genitalia (XLAG), a severe neurological condition that results in profound brain malformations, including microcephaly, absence of corpus callosum, and impairment the basal ganglia. Despite such dramatic defects, their nature origin remain largely unknown. Here, we used Arx mutant mice as model to characterize cellular molecular mechanisms underlying ganglia alterations. In these animals, early differentiation this tissue appeared normal, whereas subsequent was impaired, leading periventricular accumulation immature neurons both lateral ganglionic eminence medial (MGE). Both tangential migration toward cortex striatum radial globus pallidus were greatly reduced mutants, causing NPY+ or calretinin+ MGE. retained potential vitro but exhibited deficits morphology ability. These findings imply cell-autonomous defects underlie neuronal localization defects. Furthermore, mutants lacked large fraction cholinergic displayed strong thalamocortical projections, which major axon fiber tracts failed traverse Altogether, highlight critical functions promoting neural regulating mice, consistent phenotype XLAG patients.