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Micro RNA 9 regulates neural stem cell differentiation by controlling H es1 expression dynamics in the developing brain
Author(s) -
Tan SiokLay,
Ohtsuka Toshiyuki,
González Aitor,
Kageyama Ryoichiro
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12009
Subject(s) - biology , neural stem cell , gene knockdown , microbiology and biotechnology , rna , cellular differentiation , stem cell , untranslated region , cell culture , genetics , gene
Earlier studies show that H es1 expression is oscillatory in neural stem cells but sustained and high in the roof plate and the floor plate, and that such different dynamics of H es1 expression (oscillatory versus sustained) regulate different proliferation and differentiation characteristics of these cells (active in neural stem cells but rather dormant in roof/floor plate cells). The mechanism of how different dynamics of H es1 expression is controlled remains to be determined. Here, we found that the seed sequence of micro RNA ‐9 (mi R ‐9) is complementary to the 3′‐ UTR sequence of H es1 m RNA . Mi R ‐9 is highly expressed in the ventricular zone of the developing brain, which contains neural stem cells, but it is not expressed in the roof plate or the floor plate. Over‐expression of miR‐9 negatively regulates the Hes1 protein expression by interacting with the 3′‐ UTR of H es1 m RNA , thereby inducing cell cycle exit and neuronal differentiation. Conversely, knockdown of mi R ‐9 inhibits neuronal differentiation. Furthermore, knockdown of mi R ‐9 inhibits the oscillatory expression of H es1 m RNA in neural stem cells. These results indicate that mi R ‐9 regulates the proliferation and differentiation of neural stem cells by controlling the dynamics of H es1 expression in the developing brain.