Embryonic Nkx2.1-expressing neural precursor cells contribute to the regional heterogeneity of adult V-SVZ neural stem cells.

ABSTRACT

The adult ventricular-subventricular zone (V-SVZ) of the lateral ventricle produces several subtypes of olfactory bulb (OB) interneurons throughout life. Neural stem cells (NSCs) within this zone are heterogeneous, with NSCs located in different regions of the lateral ventricle wall generating distinct OB interneuron subtypes. The regional expression of specific transcription factors appears to correspond to such geographical differences in the developmental potential of V-SVZ NSCs. However, the transcriptional definition and developmental origin of V-SVZ NSC regional identity are not well understood. In this study, we found that a population of NSCs in the ventral region of the V-SVZ expresses the transcription factor Nkx2.1 and is derived from Nkx2.1-expressing (Nkx2.1+) embryonic precursors. To follow the fate of Nkx2.1+ cells and their progeny in vivo, we used mice with an Nkx2.1-CreER "knock-in" allele. Nkx2.1+ V-SVZ NSCs labeled in adult mice generated interneurons for the deep granule cell layer of the OB. Embryonic brain Nkx2.1+ precursors labeled at embryonic day 12.5 gave rise to Nkx2.1+ NSCs of the ventral V-SVZ in postnatal and adult mice. Thus, embryonic Nkx2.1+ neural precursors give rise to a population of Nkx2.1+ NSCs in the ventral V-SVZ where they contribute to the regional heterogeneity of V-SVZ NSCs.