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Suppression of autophagy by FIP200 inactivation results in deficient self‐renewal of neural stem cells
Author(s) -
wang chenran,
Liang Chunchi,
Guan Junlin
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb110
Subject(s) - autophagy , neural stem cell , subventricular zone , subgranular zone , conditional gene knockout , microbiology and biotechnology , biology , hippocampus , neurogenesis , olfactory bulb , neuroscience , stem cell , apoptosis , central nervous system , biochemistry , gene , phenotype
Autophagy is an evolutionarily conserved process for bulk protein degradation. Recent studies suggested a critical role of basal autophagy to maintain neuronal homeostasis. However, it remains unknown about the functions of autophagy in neural stem cells (NSCs). FIP200 is a component of the ULK1‐Atg13‐FIP200‐Atg101 complex that is essential for the induction of autophagy. By conditional inactivation of FIP200 in adult NSCs using a hGFAP‐Cre, we prove that loss of autophagy causes deficient self‐renewal of NSCs. Aggregation of ubiquitinated proteins and p62 was observed in the subventricular zone (SVZ) and the subgranular zone (SGZ), two areas NSCs predominantly reside in adult brain, in the conditional knockout (CKO) mice. Moreover, CKO mice showed substantially reduced size of olfactory bulb and hippocampus. In contrast to the increased apoptosis of neurons in cerebellum and cortex, little difference in apoptosis was found in SVZ and hippocampus between CKO and control mice. Labeling of these regions with Ki67 or BrdU indicated decreased proliferation in CKO mice. Furthermore, BrdU retention experiments indicated reduced number of NSCs in these mice. Lastly, analysis of isolated NSCs by neurosphere assay showed impaired self‐renewal of NSCs from the CKO mice. Together, these results provide strong genetic evidence for a role of autophagy in the regulation of self renewal of NSCs.