TY - JOUR
T1 - The RNA-binding protein HuD regulates neuronal cell identity and maturation
AU - Akamatsu, Wado
AU - Fujihara, Hiroaki
AU - Mitsuhashi, Takayuki
AU - Yano, Masato
AU - Shibata, Shinsuke
AU - Hayakawa, Yoshika
AU - Okano, Hirotaka James
AU - Sakakibara, Shin Ichi
AU - Takano, Hiroshi
AU - Takano, Toshiya
AU - Takahashi, Takao
AU - Noda, Tetsuo
AU - Okano, Hideyuki
PY - 2005/3/22
Y1 - 2005/3/22
N2 - Neural Hu proteins (HuB/C/D) are RNA-binding proteins that have been shown to induce neuronal differentiation activity when overexpressed in immature neural progenitor cells or undifferentiated neuronal tumors. Newly generated HuD-deficient mice exhibited a transient impaired-cranial-nerve-development phenotype at an early embryonic stage. Adult HuD-deficient mice exhibited an abnormal hind-limb reflex and poor rotarod performance. Analysis of neurosphere formation revealed that the number and self-renewal capacity of the neural stem/progenitor cells were increased in HuD-deficient mice. HuD-deficient primary neurospheres also generated a smaller number of neurons. Cohort analysis of the cellular proliferative activity by using BrdUrd and iododeoxuridine labeling revealed that the number of differentiating quiescent cells in the embryonic cerebral wall was decreased. Long-term administration of BrdUrd revealed that the number of slowly dividing stem cells in the adult subventricular zone was increased in the HuD-deficient mice. Taken together, the results suggest that HuD is required at multiple points during neuronal development, including negative regulation of proliferative activity and neuronal cell-fate acquisition of neural stem/progenitor cells.
AB - Neural Hu proteins (HuB/C/D) are RNA-binding proteins that have been shown to induce neuronal differentiation activity when overexpressed in immature neural progenitor cells or undifferentiated neuronal tumors. Newly generated HuD-deficient mice exhibited a transient impaired-cranial-nerve-development phenotype at an early embryonic stage. Adult HuD-deficient mice exhibited an abnormal hind-limb reflex and poor rotarod performance. Analysis of neurosphere formation revealed that the number and self-renewal capacity of the neural stem/progenitor cells were increased in HuD-deficient mice. HuD-deficient primary neurospheres also generated a smaller number of neurons. Cohort analysis of the cellular proliferative activity by using BrdUrd and iododeoxuridine labeling revealed that the number of differentiating quiescent cells in the embryonic cerebral wall was decreased. Long-term administration of BrdUrd revealed that the number of slowly dividing stem cells in the adult subventricular zone was increased in the HuD-deficient mice. Taken together, the results suggest that HuD is required at multiple points during neuronal development, including negative regulation of proliferative activity and neuronal cell-fate acquisition of neural stem/progenitor cells.
KW - ELAV
KW - Hu
KW - Neural stem cell
UR - http://www.scopus.com/inward/record.url?scp=20144384602&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144384602&partnerID=8YFLogxK
U2 - 10.1073/pnas.0407523102
DO - 10.1073/pnas.0407523102
M3 - Article
C2 - 15764704
AN - SCOPUS:20144384602
SN - 0027-8424
VL - 102
SP - 4625
EP - 4630
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 - 12
ER -