Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 68, Issue 10, Pages 1769-1783Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-010-0548-7
Keywords
Neural stem cells; Neural development; Positional identity; Neuronal differentiation; Transcription factors
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Funding
- Fondazione Cariplo (Italy)
- European Union [Health-F4-2008-200720, LSHB-CT-2007-037766, HEALTH-2008-B-222943]
- MRC [MC_U117570528] Funding Source: UKRI
- Medical Research Council [MC_U117570528] Funding Source: researchfish
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Neural stem (NS) cells are a self-renewing population of symmetrically dividing multipotent radial glia-like stem cells, characterized by homogeneous expansion in monolayer. Here we report that fetal NS cells isolated from different regions of the developing mouse nervous system behave in a similar manner with respect to self-renewal and neuropotency, but exhibit distinct positional identities. For example, NS cells from the neocortex maintain the expression of anterior transcription factors, including Otx2 and Foxg1, while Hoxb4 and Hoxb9 are uniquely found in spinal cord-derived NS cells. This molecular signature was stable for over 20 passages and was strictly linked to the developmental stage of the donor, because only NS cells derived from E14.5 cortex, and not those derived from E12.5 cortex, carried a consistent transcription factor profile. We also showed that traits of this positional code are maintained during neuronal differentiation, leading to the generation of electrophysiologically active neurons, even if they do not acquire a complete neurochemical identity.
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