Zic1andZic3Regulate Medial Forebrain Development through Expansion of Neuronal Progenitors

Abstract

The medial telencephalon is a source of neurons that follow distinct tangential trajectories of migration to various structures such as the cerebral cortex, striatum, and olfactory bulb. In the present study, we characterized the forebrain anomalies inZic1/Zic3compound mutant mice.Zic1andZic3were strongly expressed in the medial structures, including the septum, medial cerebral cortex, and choroid plexus. Mice homozygous for theZic1mutant allele together with the nullZic3allele showed medial forebrain defects, which were not obvious in eitherZic1orZic3single mutants. Absence of bothZic1andZic3caused hypoplasia of the hippocampus, septum, and olfactory bulb. Analysis of the cell cycle revealed that the cell cycle exit rate was increased in the septa of double mutants. Misexpression of Zic3 in the ventricular layer of the cerebral cortex inhibited neuronal differentiation. These results indicated that bothZic1andZic3function in maintaining neural precursor cells in an undifferentiated state. The functions of these genes may be essential to increasing neural cell numbers regionally in the medial telencephalon and to proper mediolateral patterning of the telencephalon.