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The Journal of Neuroscience, December 8, 2004, 24(49):11171-11181; doi:10.1523/JNEUROSCI.3248-04.2004

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Development/Plasticity/Repair
Defective Postnatal Neurogenesis and Disorganization of the Rostral Migratory Stream in Absence of the Vax1 Homeobox Gene

José Miguel Soria,¹ Paola Taglialatela,¹ Sara Gil-Perotin,³ Rossella Galli,² Angela Gritti,² José Manuel Garcia Verdugo,³ and Stefano Bertuzzi¹

¹Dulbecco Telethon Institute at Consiglio Nazionale delle Ricerche-Istituto di Tecnologie Biomediche, 20090 Segrate (Milan), Italy, ²Stem Cell Research Institute, Department of Biological and Technological Research, San Raffaele Hospital, 20132 Milan, Italy, and ³Instituto Cavanilles de Biodiversidad y Biologia Evolutiva, University of Valencia, 46980 Valencia, Spain

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 that Vax1 is strongly expressed in the SVZ and in the RMS and that, in the absence of Vax1, embryonic precursor cells proliferate 100 times more than wild-type controls, in vitro. The SVZ of Vax1^-/- 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 that Vax1 is essential for the correct differentiation of ependyma and astrocytes.

Together, these data indicate that Vax1 is a potent regulator of SVZ organization and NSC proliferation, with important consequences on postnatal neurogenesis.

Key words: subventricular zone; rostral migratory stream; neural stem cells; homeobox; development; telencephalon

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Received Aug 7, 2004; revised October 22, 2004; accepted November 1, 2004.

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