RRC ID 57129
著者 Zhang Y, Koe CT, Tan YS, Ho J, Tan P, Yu F, Sung WK, Wang H.
タイトル The Integrator Complex Prevents Dedifferentiation of Intermediate Neural Progenitors back into Neural Stem Cells.
ジャーナル Cell Rep
Abstract Mutations of the Integrator subunits are associated with neurodevelopmental disorders and cancers. However, their role during neural development is poorly understood. Here, we demonstrate that the Drosophila Integrator complex prevents dedifferentiation of intermediate neural progenitors (INPs) during neural stem cell (neuroblast) lineage development. Loss of intS5, intS8, and intS1 generated ectopic type II neuroblasts. INP-specific knockdown of intS8, intS1, and intS2 resulted in the formation of excess type II neuroblasts, indicating that Integrator prevents INP dedifferentiation. Cell-type-specific DamID analysis identified 1413 IntS5-binding sites in INPs, including zinc-finger transcription factor earmuff (erm). Furthermore, erm expression is lost in intS5 and intS8 mutant neuroblast lineages, and intS8 genetically interacts with erm to suppress the formation of ectopic neuroblasts. Taken together, our data demonstrate that the Drosophila Integrator complex plays a critical role in preventing INP dedifferentiation primarily by regulating a key transcription factor Erm that also suppresses INP dedifferentiation.
巻・号 27(4)
ページ 987-996.e3
公開日 2019-4-23
DOI 10.1016/j.celrep.2019.03.089
PII S2211-1247(19)30428-0
PMID 31018143
MeSH Animals Cell Dedifferentiation / genetics* Cell Lineage Drosophila / cytology* Drosophila / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila Proteins / physiology* Gene Expression Regulation Neural Stem Cells / cytology*
IF 7.815
引用数 1
リソース情報
ショウジョウバエ DGRC#114705