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Forced expression of the motor neuron determinant HB9 in neural stem cells affects neurogenesis.
Bréjot T., Blanchard S., Hocquemiller M., Haase G., Liu S., Nosjean A., Heard J. M., Bohl D.
Experimental Neurology 198, 1 (2006) 167-82 - http://www.hal.inserm.fr/inserm-00483907
(16434037)
Forced expression of the motor neuron determinant HB9 in neural stem cells affects neurogenesis.
Thomas Bréjot1, Stéphane Blanchard1, Michaël Hocquemiller1, Georg Haase2, Song Liu1, Anne Nosjean1, Jean Michel Heard1, Delphine Bohl () 1
1 :  Rétrovirus et Transfert Génétique
INSERM : U622 – Institut Pasteur de Paris
28, Rue du Docteur Roux 75724 PARIS CEDEX 15
France
2 :  Epilepsie et ischémie cérébrale
http://www.inmed.univ-mrs.fr/
INSERM : U29 – Université de la Méditerranée - Aix-Marseille II
Inst Neurobiologie de La Mediterranee 163, Avenue de Luminy 13273 MARSEILLE CEDEX 09
France
In contrast to mouse embryonic stem cells and in spite of overlapping gene expression profiles, neural stem cells (NSCs) isolated from the embryonic spinal cord do not respond to physiological morphogenetic stimuli provided by Sonic hedgehog and retinoic acid and do not generate motor neurons upon differentiation. Transcription factors expressed in motor neuron progenitors during embryogenesis include Pax6, Ngn2, Nkx6.1 and Olig2, whose expression precedes that of factors specifying motor neuron fate, including HB9, Islet1 and LIM3. We showed that all these factors were present in neural progenitors derived from mouse ES cells, whereas NSCs derived from the rat embryonic spinal cord expressed neither HB9 nor Islet1 and contained low levels of Nkx6.1 and LIM3. We constructed a lentivirus vector to express HB9 and GFP in NSCs and examined the consequences of HB9 expression on other transcription factors and cell differentiation. Compared to cell expressing GFP alone, NSCs expressing GFP and HB9 cycled less rapidly, downregulated Pax6 and Ngn2 mRNA levels, produced higher proportions of neurons in vitro and lower numbers of neurons after transplantation in the spinal cord of recipient rats. Oligodendrocytic and astrocytic differentiations were not affected. HB9 expressing NSCs did not express Islet1 or upregulate LIM3. They neither responded to Sonic hedgehog and retinoic acid nor produced cholinergic neurons. We concluded that forced HB9 expression affected neurogenesis but was not sufficient to confer motor neuron fate to NSCs.
Sciences du Vivant/Biologie cellulaire
Anglais
0014-4886

Articles dans des revues avec comité de lecture
10.1016/j.expneurol.2005.11.026
Experimental Neurology (Exp Neurol)
Publisher Elsevier
ISSN 0014-4886 (eISSN : 1090-2430)
internationale
03/2006
24/01/2006
198
1
167-82

2' – 3'-Cyclic-Nucleotide Phosphodiesterases – Animals – Basic Helix-Loop-Helix Transcription Factors – Cell Count – Cell Differentiation – Cell Proliferation – Cells – Cultured – Embryo – Mammalian – Eye Proteins – Functional Laterality – Gene Expression – Gene Expression Regulation – Developmental – Glial Fibrillary Acidic Protein – Green Fluorescent Proteins – Homeodomain Proteins – Humans – Immunohistochemistry – Indoles – Intermediate Filament Proteins – Mice – Nerve Tissue Proteins – Neurofilament Proteins – Neurons – Paired Box Transcription Factors – RNA – Messenger – Rats – Inbred F344 – Repressor Proteins – Reverse Transcriptase Polymerase Chain Reaction – Spinal Cord – Stem Cells – Transcription Factors – Transfection – Tubulin – Tyrosine 3-Monooxygenase