title: Differential expression of cell fate determinants in neurons and glial cells of adult mouse spinal cord after compression injury.
abstract: Cellular responses after spinal cord injury include activation of astrocytes, degeneration of neurons and oligodendrocytes, and reactions of the ependymal layer and meningeal cells. Because it has been suggested that tissue repair partially recapitulates morphogenesis, we have investigated the expression of several developmentally prominent molecules after spinal cord injury of adult mice where neurogenesis does not occur after injury. Cell fate determinants Numb, Notch-1, Shh and BMPs are abundantly expressed during development but mostly decline in the adult. In the present study, we investigated whether these genes are triggered by spinal cord injury as a sign of attempted recapitulation of development. Expression of Numb, Notch, Shh, BMP2/4 and Msx1/2 was analysed in the adult mouse spinal cord after compression injury by in situ hybridization up to 1 month after injury. The mRNA expression levels of Notch-1, Numb, Shh, BMP4 and Msx2 increased in the grey matter and/or white matter and in the ependyma rostral and caudal to the lesion site after injury. However, BMP2 and Msx1 were not up-regulated. Combining immunohistochemistry of cell type-specific markers with in situ hybridization we found that all the up-regulated genes were expressed in neurons. Moreover, Numb, BMP4 and Msx2 were also expressed by GFAP-positive astrocytes, while Shh was expressed by MBP-positive oligodendrocytes. In conclusion, the cell fate determinants Notch-1, Numb, Shh, BMP4 and Msx2 are expressed in neurons and/or glial cells after injury in a time-dependent manner, suggesting that these genes reflect to some extent an endogenous self-repair potential by recapitulating some features of development.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Soo-Yuen
authors.initials: SY
authors.lastname: Leong
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D013117:Spinal Cord Compression / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C497762:Notch1 protein, mouse; C106293:Numb protein, mouse; D051881:Receptor, Notch1; C465570:Shh protein, mouse; D015534:Trans-Activators; D010751:Phosphopyruvate Hydratase