TY - JOUR
T1 - microRNA-34a regulates neurite outgrowth, spinal morphology, and function
AU - Agostini, Massimiliano
AU - Tucci, Paola
AU - Steinert, Joern R.
AU - Shalom-Feuerstein, Ruby
AU - Rouleau, Matthieu
AU - Aberdam, Daniel
AU - Forsythe, Ian D.
AU - Young, Kenneth W.
AU - Ventura, Andrea
AU - Concepcion, Carla P.
AU - Han, Yoon Chi
AU - Candi, Eleonora
AU - Knight, Richard A.
AU - Mak, Tak W.
AU - Melino, Gerry
PY - 2011/12/27
Y1 - 2011/12/27
N2 - 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.
AB - 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.
KW - Cell death
KW - Hippocampus
KW - Neuronal differentiation
KW - Synaptogenesis
UR - http://www.scopus.com/inward/record.url?scp=84855495456&partnerID=8YFLogxK
U2 - 10.1073/pnas.1112063108
DO - 10.1073/pnas.1112063108
M3 - مقالة
SN - 0027-8424
VL - 108
SP - 21099
EP - 21104
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -