TY - JOUR
T1 - Defective postnatal neurogenesis and disorganization of the rostral migratory stream in absence of the Vax1 homeobox gene
AU - Soria, José Miguel
AU - Taglialatela, Paola
AU - Gil-Perotin, Sara
AU - Galli, Rossella
AU - Gritti, Angela
AU - Verdugo, J. M G
AU - Bertuzzi, Stefano
PY - 2004/12/8
Y1 - 2004/12/8
N2 - 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.
AB - 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.
KW - Development
KW - Homeobox
KW - Neural stem cells
KW - Rostral migratory stream
KW - Subventricular zone
KW - Telencephalon
UR - http://www.scopus.com/inward/record.url?scp=10944221944&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10944221944&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3248-04.2004
DO - 10.1523/JNEUROSCI.3248-04.2004
M3 - Article
C2 - 15590934
AN - SCOPUS:10944221944
VL - 24
SP - 11171
EP - 11181
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 49
ER -