We found that all parts of the telencephalic neuroepithelium, including the medial ganglionic eminence and lateral ganglionic eminence (LGE) and the cerebral cortex, contribute multipotent, self-renewing stem cells to the adult SVZ. Both the LGE- and cortex-derived stem cells generate RMS neuroblasts and are responsible for generating olfactory interneurons throughout life.
Nkx2.1-Cre (to label the MGE), Gsh2-Cre (LGE and MGE), Emx1-Cre (cerebral cortex), and Dbx1-Cre (corticostriatal sulcus, which may be reffered as dorsal LGE, as a boundary between palium and ventral parts)
Notice the figure O, the correspondence between embryonic structures and postnal structures.
Adult neural stem cells have been described as a subpopulation of SVZ astrocytes because of their morphology and the fact that they express the astrocyte marker, glial fibrillary acidic protein (GFAP) (Doetsch et al., 1999a; Laywell et al., 2000). It is now well established that the slowly dividing SVZ stem cells generate rapidly dividing neuronal progenitors (transit amplifying cells) that in turn generate postmitotic neuroblasts. These migrate forwards along the rostral migratory stream (RMS) into the olfactory bulb, where they give rise to various subtypes of olfactory interneurons continuously throughout life (for review, see Lledo et al., 2006). However, it is still unclear whether the SVZ contains a heterogeneous collection of neural stem cells with different neurogenic potentials or whether cell fate restriction occurs later, within the RMS or the olfactory bulb.
Neuroepithelial precursors in most parts of the embryonic telencephalon have a similar radial morphology and express antigenic markers characteristic of radial glia (Noctor et al., 2002; Malatesta et al., 2003; Anthony et al., 2004). However, there are also regional differences in gene expression, including regionally restricted expression of transcription factors (Kriegstein and Götz, 2003). For example, the medial ganglionic eminence (MGE) expresses Nkx2.1, the MGE and the lateral ganglionic eminence (LGE) express Gsh2, the corticostriatal sulcus expresses Dbx1, and the developing cortex expresses Emx1. As development proceeds, the neuroepithelial germinal zone [ventricular zone (VZ)] regresses and a relatively small proportion of neural stem cells persists in the SVZ of the adult forebrain. The relative contributions of different parts of the embryonic VZ to the adult SVZ have not yet been established, although the bulk of previous evidence suggests that adult stem cells are descendants of the LGE (embryonic striatum). For example, transcription factors that are expressed in the dorsal LGE of the embryo, such as Dlx1/2, Er81, Gsh2, and Pax6, are also present within the adult SVZ and RMS (Parmar et al., 2003; Stenman et al., 2003; Kohwi et al., 2005). In addition, viral lineage tracing of radial glia in the perinatal LGE has demonstrated that some of the progeny of these cells come to reside in the postnatal SVZ and contribute significantly to the adult neurosphere-forming activity (Merkle et al., 2004). Recent evidence supports the contribution of embryonic cortical (Emx-1-expressing) progenitors to generating the adult SVZ (Tamamaki, 2005; Willaime-Morawek et al., 2006; Ventura and Goldman, 2007). However, it is still unknown whether other parts of the embryonic VZ such as the MGE contribute cells to the adult SVZ or, if so, whether adult SVZ cells retain their previously established positional and functional identities into adulthood.
Here, we have examined the origins of adult SVZ stem cells by Cre-lox fate mapping of the embryonic telencephalic neuroepithelium, using Nkx2.1-Cre, Gsh2-Cre, Dbx1-Cre, Emx1-Cre, and Emx1-CreERT2 transgenic mice (Fogarty et al., 2005; Kessaris et al., 2006). We found that the MGE, LGE, and the embryonic cortex all generate cells that populate different parts of the adult SVZ and exhibit the in vitro characteristics of multipotent neural stem cells. Both the LGE- and cortex-derived stem cells generate RMS neuroblasts and are responsible for generating olfactory interneurons throughout life. However, these two stem cell populations make unequal contributions to adult neurogenesis. Cortex-derived stem cells, despite being the minority, generate the majority of calretinin-positive interneurons but none of the calbindin-positive interneurons. LGE-derived stem cells generate all of the adult-born calbindin-positive interneurons for the olfactory glomerulus.
