Defective Postnatal Neurogenesis and Disorganization of the Rostral Migratory Stream in Absence of theVax1Homeobox Gene

• DOI: 10.1523/jneurosci.3248-04.2004
• Publication Date: 2004-12-08T21:54:14Z
• Authors: José Miguel Soria; Paola Taglialatela; Sara Gil-Perotin; Rossella Galli; Angela Gritti; José Manuel Garci...; Stefano Bertuzzi
• Keywords: Homeodomain Proteins; Mice, Knockout; Telencephalon; 0303 health sciences; Stem Cells; Neuropeptides; Genes, Homeobox; Gene Expression Regulation, Developmental; Cell Differentiation; Mice, Transgenic; Nerve Tissue Proteins; Olfactory Bulb; DNA-Binding Proteins; Mice; 03 medical and health sciences; Cell Movement; Animals; Cell Proliferation; Transcription Factors

The subventricular zone (SVZ) is one of the sources of adult neural stem cells (ANSCs) in the mouse brain. Precursor cells proliferate in the SVZ and migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into granule and periglomerular cells. Few transcription factors are known to be responsible for regulating NSC proliferation, migration, and differentiation processes; even fewer have been found to be responsible for the organization of the SVZ and RMS. For this reason, we studied the ventral anterior homeobox (Vax1) gene in NSC proliferation and in SVZ organization. We found thatVax1is strongly expressed in the SVZ and in the RMS and that, in the absence ofVax1, embryonic precursor cells proliferate 100 times more than wild-type controls,in vitro. The SVZ ofVax1-/-brains is hyperplastic and mostly disorganized, and the RMS is missing, causing a failure of precursor cell migration to the OBs, which as a result are severely hypoplastic. Moreover, we found thatVax1is essential for the correct differentiation of ependyma and astrocytes.Together, these data indicate thatVax1is a potent regulator of SVZ organization and NSC proliferation, with important consequences on postnatal neurogenesis.