Authors: | Agostini, M.; Tucci, P.; Steinert, J. R.; Shalom-Feuerstein, R.; Rouleau, M.; Aberdam, D.; Forsythe, I. D.; Young, K. W.; Ventura, A.; Concepcion, C. P.; Han, Y. C.; Candi, E.; Knight, R. A.; Mak, T. W.; Melino, G. |
Article Title: | microRNA-34a regulates neurite outgrowth, spinal morphology, and function |
Abstract: | The p53 family member TAp73 is a transcription factor that plays a key role in many biological processes, including neuronal development. In particular, wehave shown that p73 drives the expression of miR-34a, but not miR-34b and c, in mouse cortical neurons. miR-34a in turn modulates the expression of synaptic targets including synaptotagmin-1 and syntaxin-1A. Here we show that this axis is retained in mouse ES cells committed to differentiate toward a neurological phenotype. Moreover, overexpression of miR-34a alters hippocampal spinal morphology, and results in electrophysiological changes consistent with a reduction in spinal function. Therefore, the TAp73/miR-34a axis has functional relevance in primary neurons. These data reinforce a role for miR-34a in neuronal development. |
Keywords: | unclassified drug; nonhuman; animal cell; mouse; phenotype; animals; mice; mice, knockout; animal tissue; cell death; microrna; embryo; embryonic stem cell; transcription factor; cell differentiation; protein p53; morphology; nuclear proteins; rna; blotting, western; spine; western blotting; embryonic stem cells; real time polymerase chain reaction; micrornas; nerve cell differentiation; electrophysiology; nervous system; hippocampus; neuronal differentiation; synaptotagmin i; brain cell; nerve fiber growth; syntaxin 1; synaptogenesis; microrna 34a; real-time polymerase chain reaction; bicuculline; dizocilpine; strychnine; neurites |
Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
Volume: | 108 |
Issue: | 52 |
ISSN: | 0027-8424 |
Publisher: | National Academy of Sciences |
Date Published: | 2011-01-01 |
Start Page: | 21099 |
End Page: | 21104 |
Language: | English |
DOI: | 10.1073/pnas.1112063108 |
PROVIDER: | scopus |
PMCID: | PMC3248521 |
PUBMED: | 22160706 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 1 March 2012" - "CODEN: PNASA" - "Source: Scopus" |