The Integrator Complex Prevents Dedifferentiation of Intermediate Neural Progenitors back into Neural Stem Cells.

Cell Rep

Neuroscience & Behavioral Disorders Programme, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. Electronic address:

Published: April 2019

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.

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http://dx.doi.org/10.1016/j.celrep.2019.03.089DOI Listing

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