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Neurodevelopmental abnormalities in neurosphere‐derived neural stem cells from SMN‐depleted mice
Author(s) -
Shafey Dina,
MacKenzie Alex E.,
Kothary Rashmi
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21743
Subject(s) - neurosphere , sma* , spinal muscular atrophy , nestin , neural stem cell , neurite , neuroscience , biology , motor neuron , microbiology and biotechnology , spinal cord , stem cell , cellular differentiation , gene , adult stem cell , genetics , mathematics , combinatorics , in vitro
Spinal muscular atrophy (SMA) is a genetic disorder caused by depletion of survival motor neuron (SMN) protein and characterized by degeneration of α‐motor neurons in the spinal cord. We investigated the morphology and differentiation of neurosphere‐derived neural stem cells (NSCs) generated from the brains of a hypomorphic series of SMA mice. Neurospheres from the Smn −/− ;SMN2 mice, which represent a model of very severe SMA, produced NSCs with increased proliferation during growth and differentiation. These cells produced fewer Tuj1‐positive neuronal cells, which displayed morphological alterations and had fewer and shorter neurites. The decrease in the number of Tuj1‐positive cells was not a result of enhanced apoptosis but was accompanied by an increase in the number of nestin‐positive cells. These results provide insight into the most severe model of SMA, in which SMN is nearly completely depleted, and suggest that SMN has a role in neurodevelopment as well as in neuromaintenance. Our work raises the possibility that SMN depletion affects neurodevelopment and neuromaintenance to varying extents, leading to SMA pathogenesis. © 2008 Wiley‐Liss, Inc.