Biology subjects

Knoblich, J.

Publications and source records attributed to Knoblich, J..

2 recordsLinked to original sources

bioRxiv2019

Dynamics of activating and repressive histone modifications in Drosophila neural stem cell lineages and brain tumors

During central nervous system (CNS) development, spatiotemporal gene expression programs mediate specific lineage decisions to generate neuronal and glial cell types from neural stem cells (NSCs). However, little is known about the epigenetic landscape underlying these highly complex developmental events. Here, we perform ChIP-seq on distinct subtypes of Drosophila FACS-purified neural stem cells (NSCs) and their differentiated progeny to dissect the epigenetic changes accompanying the major lineage decisions in vivo. By analyzing active and repressive histone modifications, we show that stem cell identity genes are silenced during differentiation by loss of their activating marks and not via repressive histone modifications. Our analysis also uncovers a new set of genes specifically required for altering lineage patterns in type II neuroblasts, one of the two main Drosophila NSC identities. Finally, we demonstrate that this subtype specification in NBs, unlike NSC differentiation, requires Polycomb-group (PcG)-mediated repression.\n\nSummary statementDynamic epigenetic landscape of Drosophila neural stem cell lineages.

developmental biology↗

bioRxiv2019

The transcription factor Odd-paired regulates temporal identity in transit-amplifying neural progenitors via an incoherent feed-forward loop

Neural progenitors undergo temporal patterning to generate diverse neurons in a chronological order. This process is well-studied in the developing Drosophila brain and conserved in mammals. During larval stages, intermediate neural progenitors (INPs) serially express Dichaete (D), grainyhead (Grh) and eyeless (Ey/Pax6), but how the transitions are regulated is not precisely understood. Here, we developed a method to isolate transcriptomes of INPs in their distinct temporal states to identify a complete set of temporal patterning factors. Our analysis identifies odd-paired (opa), as a key regulator of temporal patterning. Temporal patterning is initiated when the SWI/SNF complex component Osa induces D and its repressor Opa at the same time but with distinct kinetics. Then, high Opa levels repress D to allow Grh transcription and progress to the next temporal state. We propose that Osa and its target genes opa and D form an incoherent feedforward loop (FFL) and a new mechanism allowing the successive expression of temporal identities.

developmental biology↗