The Ets protein Pointed P1 represses Asense expression in type II neuroblasts by activating Tailless.

Rui Chen,Xiaobing Deng,Sijun Zhu,Hongyan Wang

doi:10.1371/journal.pgen.1009928

Rui Chen, Xiaobing Deng + Show 2 more

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https://doi.org/10.1371/journal.pgen.1009928

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Journal: PLoS genetics	Publication Date: Jan 31, 2022
Citations: 4	License type: CC BY 4.0

Affiliation: SUNY Upstate Medical University

Abstract

Intermediate neural progenitors (INPs) boost the number and diversity of neurons generated from neural stem cells (NSCs) by undergoing transient proliferation. In the developing Drosophila brains, INPs are generated from type II neuroblasts (NBs). In order to maintain type II NB identity and their capability to produce INPs, the proneural protein Asense (Ase) needs to be silenced by the Ets transcription factor pointed P1 (PntP1), a master regulator of type II NB development. However, the molecular mechanisms underlying the PntP1-mediated suppression of Ase is still unclear. In this study, we utilized genetic and molecular approaches to determine the transcriptional property of PntP1 and identify the direct downstream effector of PntP1 and the cis-DNA elements that mediate the suppression of ase. Our results demonstrate that PntP1 directly activates the expression of the transcriptional repressor, Tailless (Tll), by binding to seven Ets-binding sites, and Tll in turn suppresses the expression of Ase in type II NBs by binding to two hexameric core half-site motifs. We further show that Tll provides positive feedback to maintain the expression of PntP1 and the identity of type II NBs. Thus, our study identifies a novel direct target of PntP1 and reveals mechanistic details of the specification and maintenance of the type II NB identity by PntP1.

Highlights

Constructing a functional nervous system requires generation of a large number of diverse types of neurons and glia during development
Type II neuroblasts (NBs) are the neural stem cells (NSCs) in Drosophila central brains that produce neurons by generating intermediate neural progenitors (INPs) to boost brain complexity, as mammalian NSCs do during the development of neocortex
The key to the generation of INPs from type II NBs is the suppression of proneural protein Asense (Ase) in type II NBs by the E26 transformation-specific (Ets) family transcription factor Pointed P1 (PntP1), but how PntP1 suppresses Ase expression remains unclear

Summary

Introduction

Constructing a functional nervous system requires generation of a large number of diverse types of neurons and glia during development. Misexpression of PntP1 is sufficient to transform type I NBs into type II NBs by suppressing Ase expression and promote the production of INPs. The transformed type II NB lineages are susceptible to tumorigenic overproliferation resulting from loss of tumor suppressors such as Brain Tumor (Brat) and Earmuff (Erm), the latter of which is a direct downstream target of PntP1 in immature INPs (imINPs) [10,14,15,16]. The transformed type II NB lineages are susceptible to tumorigenic overproliferation resulting from loss of tumor suppressors such as Brain Tumor (Brat) and Earmuff (Erm), the latter of which is a direct downstream target of PntP1 in immature INPs (imINPs) [10,14,15,16] It is not clear if PntP1 acts as a transcriptional repressor to directly suppress Ase expression or acts as a transcriptional activator to suppress Ase indirectly by activating the expression of other transcription factor(s)

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