RRC ID 40045
著者 Narbonne-Reveau K, Lanet E, Dillard C, Foppolo S, Chen CH, Parrinello H, Rialle S, Sokol NS, Maurange C.
タイトル Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila.
ジャーナル Elife
Abstract Pediatric neural tumors are often initiated during early development and can undergo very rapid transformation. However, the molecular basis of this early malignant susceptibility remains unknown. During Drosophila development, neural stem cells (NSCs) divide asymmetrically and generate intermediate progenitors that rapidly differentiate in neurons. Upon gene inactivation, these progeny can dedifferentiate and generate malignant tumors. Here, we find that intermediate progenitors are prone to malignancy only when born during an early window of development while expressing the transcription factor Chinmo, and the mRNA-binding proteins Imp/IGF2BP and Lin-28. These genes compose an oncogenic module that is coopted upon dedifferentiation of early-born intermediate progenitors to drive unlimited tumor growth. In late larvae, temporal transcription factor progression in NSCs silences the module, thereby limiting mitotic potential and terminating the window of malignant susceptibility. Thus, this study identifies the gene regulatory network that confers malignant potential to neural tumors with early developmental origins.
巻・号 5
公開日 2016-6-14
DOI 10.7554/eLife.13463
PII e13463
PMID 27296804
PMC PMC4907696
MeSH Animals Carcinogenesis* Cell Differentiation* Cell Proliferation* Disease Susceptibility* Drosophila / embryology* Drosophila Proteins / biosynthesis Nerve Tissue Proteins / biosynthesis Neural Stem Cells / physiology* RNA-Binding Proteins / biosynthesis Time Factors
IF 7.08
引用数 30
リソース情報
ショウジョウバエ 17156R-1