AUF1 and Hu proteins in the developing rat brain: implication in the proliferation and differentiation of neural progenitors.
Posttranscriptional events such as RNA stabilization are important for cell differentiation, but little is known about the impact of AU-rich binding proteins (AUBPs) on the fate of neural cells. Expression of destabilizing AUBPs such as AUF1 and neuronal-specific stabilizing proteins such as HuB, HuC and HuD was therefore analyzed in the developing central nervous system. Real-time RT-PCR indicated a specific developmental pattern in the postnatal cerebellum, with a progressive down-regulation of AUF1 from P1, whereas HuB was strongly up-regulated at about P7. These changes were accompanied by a progressive increase in AUF1p45 and the disappearance of one HuB isoform from P15, suggesting particular roles for these AUBPs in the developing cerebellum. AUF1 was detected in the three main cerebellar layers, whereas Hu proteins were found only in postmitotic neurons. A role for Hu proteins in the early stages of neuronal differentiation is further supported by arrest of cell proliferation following induction of HuB or HuD expression in a neural stem cell line. The decrease in nestin expression suggest that HuD, but not HuB, favors the transition of neural progenitors into early neuroblasts, but other factors are most probably required for their full differentiation into neurons, insofar as GAP-43 was not detected in HuD-transfected cells. These data suggest critical roles for HuB at the very earliest stages of neuronal differentiation, such as cell cycle exit, and HuD might also be involved in the transition of neural progenitors into early neuroblasts. Taken together, the present results strengthen the importance of AUBPs in brain ontogenesis.
Hambardzumyan
Dolores
D
INSERM U643, Nantes, France.
Sergent-Tanguy
Solène
S
Thinard
Reynald
R
Bonnamain
Virginie
V
Masip
Manuel
M
Fabre
Annabelle
A
Boudin
Hélène
H
Neveu
Isabelle
I
Naveilhan
Philippe
P
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism*; D000067777:ELAV-Like Protein 2; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051959:ELAV Proteins; D000067777:ELAV-Like Protein 2; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; C490170:Elavl2 protein, rat; C490262:Elavl3 protein, rat; C000594136:Elavl4 protein, rat; D019922:GAP-43 Protein; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630988:Hnrnpd protein, rat; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D020033:Protein Isoforms; D012333:RNA, Messenger