Differential express of Transcription factors after SC injury

Differential express of Transcription factors after SC injury

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Differential expression of cell fate determinants in neurons and glial cells of adult mouse spinal cord after compression injury Jian Chen, Soo-Yuen Leong and Melitta Schachner Zentrum fu ¨r Molekulare Neurobiologie, Universita ¨t Hamburg, Martinistrasse 52, 20246 Hamburg, Germany Keywords : bone morphogenetic protein, mouse, Msx, Notch-1, Numb, Sonic hedgehog, spinal cord 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-speciFc 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 G±AP-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 re²ect to some extent an endogenous self- repair potential by recapitulating some features of development. Introduction In contrast to the peripheral nervous system which shows good regrowth of neurites after axotomy, the injured spinal cord of adult mammals has only limited ability. However, more recent observations implicate the inherent capacity for self-repair of the adult mammalian spinal cord in partial functional recovery. These studies also suggest that the spared and or regenerated spinal functions after injury may be attributed to the spontaneous formation or rearrangement of intraspinal circuits that are able to partially compensate for functional loss (Weidner et al ., 2001; Bareyre et al ., 2004). The mechanistic basis for the reconstruction of neural circuits may include neuronal survival, outgrowth of new neurites and reorganization of neural circuits close to and at some distance from the lesion site, involving not only neurons but also glial cells and in particular astrocytes, which are
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This note was uploaded on 09/29/2010 for the course BIOLOGY BISP 194 taught by Professor Hermann during the Fall '10 term at UCSD.

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Differential express of Transcription factors after SC injury

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