Neurogenesis of heterotopic gray matter in the brain of the microcephalic mouse

Neurogenesis of heterotopic gray matter in the brain of the microcephalic m ouse prenatally exposed to X-rays at embryonic day 13 (E13) was studied imm unohistochemically. Bromodeoxyuridine (BrdU) as a marker to label the migra ting position of neuroblasts generated at various embryonic stages showed t hat no "inside-out" pattern of neuronal migration occurred in the heterotop ic cell mass similar to that seen in the laminated cortex. Further results in which midkind (MK) immunoreactive radial glial fibers did not appear in the heterotopic cell mass demonstrated that heterotopia formed in the absen ce of radial glia system. Different types of cells (pyramidal and non-pyram idal neurons) in the heterotopic cell mass were identified with immunoreact ivity for anti-parvalbumin and anti-calbindin D-28K antibodies in addition to current histological methods. Two major types of neurons were mixed toge ther with random distribution in the heterotopic cell mass. This finding in dicates that irradiation might have no selective effects on the precursors of pyramidal and non-pyramidal neurons. Moreover, anti-glial fibrillary aci dic protein (GFAP) immunostaining showed that numerous astrocytes were pres ent in the heterotopic cell mass. The fact that astrocytes appeared in the heterotopia without the transition from classic radial glial cells to astro cytes suggests that astrocytes might be generated directly from a separate astroglial precursor. (C) 2001 Wiley-Liss, Inc.