Cellular and Molecular Life Sciences

, Volume 68, Issue 10, pp 1769–1783 | Cite as

Preservation of positional identity in fetus-derived neural stem (NS) cells from different mouse central nervous system compartments

  • Marco Onorati
  • Maurizio Binetti
  • Luciano Conti
  • Stefano Camnasio
  • Giovanna Calabrese
  • Ilaria Albieri
  • Francesca Di Febo
  • Mauro Toselli
  • Gerardo Biella
  • Ben Martynoga
  • Francois Guillemot
  • G. Giacomo Consalez
  • Elena CattaneoEmail author
Research Article


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.


Neural stem cells Neural development Positional identity Neuronal differentiation Transcription factors 



Brain-derived neurotrophic factor


Central nervous system




Epidermal growth factor


Embryonic stem cell


Fibroblast growth factor 2


γ-Aminobutyric acid


Growth-associated protein 43


Glial fibrillary acid protein


Lateral ganglionic eminence


Microtubule-associated protein 2


Medial ganglionic eminence



NS cells

Radial glia-like neural stem cells




Sonic hedgehog


Subventricular zone



This research was supported by initial funding from Fondazione Cariplo (Italy) in the context of the awarded N.O.B.E.L. (Operational Network for Biomedicine par Excellence in Lombardy) project entitled “A genetic toolkit for the analyses of neural stem cells—acronym: Mouse NS-toolkit”. This work is also supported by EuroSystem (FP7, European Union Health-F4-2008-200720), Neuroscreen (FP6, European Union LSHB-CT-2007-037766), and NeuroStemcell (FP7, European Union HEALTH-2008-B-222943). The laboratory also acknowledges the contribution of Unicredit Banca S.p.A. (Italy) and of Tavola Valdese (Italy).

Supplementary material

18_2010_548_MOESM1_ESM.jpg (751 kb)
Figure S1. RT–PCR analysis of selected neural progenitor/stem cell markers (JPEG 750 kb)
18_2010_548_MOESM2_ESM.jpg (1.8 mb)
Figure S2. Immunofluorescence characterization of E14.5 neocortex-derived NSCs. Self-renewing NS14CX cells homogeneously showed double immunoreactivity for Nestin/Vimentin and SOX2/PAX6 (JPEG 1804 kb)
18_2010_548_MOESM3_ESM.jpg (2 mb)
Figure S3. Immunofluorescence characterization of 3 different clones of NS cells derived from E12.5 neocortex (NS12CX) and 3 clones of NS cells derived from E12.5 spinal cord (NS12SC). Self-renewing NS cell clones homogeneously express the typical NS cell markers Nestin, BLBP, RC2, Vimentin, and OLIG2 (JPEG 2075 kb)
18_2010_548_MOESM4_ESM.jpg (646 kb)
Figure S4. Neuronal differentiation of NS12SC. This image shows a GAP-43-positive neuron derived from NS12SC cells differentiated for 23 d (JPEG 646 kb)
18_2010_548_MOESM5_ESM.jpg (579 kb)
Figure S5. RT–PCR analysis of a subset of neurotransmitter receptors, described in striatal and spinal cord neurons in vivo. Neither proliferating (P) nor differentiating (D) NS cells expressed functional glutamatergic, glycinergic, or cholinergic receptors, even if the muscarinic receptor (Chrm4) was detectable (JPEG 579 kb)


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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Marco Onorati
    • 1
  • Maurizio Binetti
    • 1
  • Luciano Conti
    • 1
  • Stefano Camnasio
    • 1
  • Giovanna Calabrese
    • 2
  • Ilaria Albieri
    • 2
  • Francesca Di Febo
    • 3
  • Mauro Toselli
    • 3
  • Gerardo Biella
    • 3
  • Ben Martynoga
    • 4
  • Francois Guillemot
    • 4
  • G. Giacomo Consalez
    • 2
  • Elena Cattaneo
    • 1
    Email author
  1. 1.Department of Pharmacological Sciences and Center for Stem Cell ResearchUniversità degli Studi di MilanoMilanItaly
  2. 2.San Raffaele Scientific Institute and Università Vita-Salute San RaffaeleMilanItaly
  3. 3.Department of Cellular and Molecular Physiological and Pharmacological SciencesUniversity of PaviaPaviaItaly
  4. 4.National Institute for Medical ResearchLondonUK

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