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ISDN2012_0210: Characterization of pro‐ and anti‐regenerative processes in the neonatal mouse brain
Author(s) -
Maxwell K.A.,
Butt R.H.,
Coorssen J.R.,
Dyck R.H.
Publication year - 2012
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2012.10.033
Subject(s) - neuroscience , characterization (materials science) , chemistry , biology , nanotechnology , materials science
INSERM U1051, Université Montpellier 2, Institut des Neurosciences de Montpellier, France E-mail address: hugnot@univ-montp2.fr (J.P. Hugnot). In the brain, specific signalling pathways localized in highly organized regions called niches, allow the persistence of a pool of stem and progenitor cells that generate new neurons and glial cells in adulthood. Much less is known on the spinal cord central canal niche where a sustained adult neurogenesis is not observed. Far from being a simple layer of homogenous cells, we found, both in man and in rodents, that this region is composed of several cell types localized at specific locations, expressing characteristic markers and with different morphologies and functions. Notably the mouse niche contains a subset of Dcx+ Nkx6.1+ neuronal cells sending processes into the lumen and another subpopulation of GFAP+ cells that extends radial processes into the parenchyma. These GFAP+ cells are more frequently observed in the dorsal or ventral central canal parts, either in an ependymal or subependymal position. Using a hGFAP-GFP mouse line, we found that these GFAP+ cells express FoxJ1 and are the main source of adult spinal cord stem cells. Screening of online gene expression databases (notably Allen brain and Gensat atlas) and extensive immunodetections allowed us to identify in the central canal region, the expression of several genes involved in the Notch (Jagged, Hes1), Wnt (Wnt7a, Fzd3), BMP (DAN, BMP6) and Hedgehog (SHH) pathways. We also found that cells in this region, notably the GFAP+ cells, highly expressed Zeb1 (also known as -EF1, TCF8, AREB6), a zinc finger-homeodomain transcription factor which has been described as an important regulator of epithelial-mesenchymal transition. Zeb1 and 2 are expressed by neurosphere cells derived from the adult spinal cord and are required for neurosphere formation and expansion. In depth characterization of the spinal cord niche in man and rodents constitutes an essential framework to understand the role of these cells in spinal cord physiology and damages.