A Notch-dependent transcriptional mechanism controls expression of temporal patterning factors in Drosophila medulla
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ABSTRACT:
PROVIDER: PRJNA779739 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16922127.fastq.gz | Fastqsanger.gz | |||
| SRR16922128.fastq.gz | Fastqsanger.gz | |||
| SRR16922129.fastq.gz | Fastqsanger.gz | |||
| SRR16922130.fastq.gz | Fastqsanger.gz | |||
| SRR16922131.fastq.gz | Fastqsanger.gz |
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Project description:In this work, we show that the expression of one temporal transcription factor(TTF), Sloppy-paired (Slp), in the Drosophila medulla TTF cascade, is regulated directly by two other TTFs and the Notch signaling pathway. We show that the previous TTF, Eyeless, another TTF Scro and Su(H)/NICD regulate the transcription of Slp through binding to two cis-regulatory elements in the slp locus. Slp expression is delayed when Notch signaling is lost or when cell cycle progression is blocked, which also cause loss of Notch signaling. Furthermore, we show that supplying Notch signaling can rescue the delayed Slp expression in cell-cycle arrested neuroblasts. Thus our work demonstrates that Notch signaling cooperates with TTFs to promote the progression of the TTF transcriptional cascade.
2022-08-10 | GSE188643 | GEO
Project description:During development, neural stem cells are temporally patterned to sequentially generate a variety of neural types before exiting the cell cycle. Temporal patterning is well-studied in Drosophila, where neural stem cells called neuroblasts sequentially express cascades of Temporal Transcription Factors (TTFs) to control the birth-order dependent neural specification. However, currently known TTFs were mostly identified through candidate antibody screening and may not be complete. In addition, many fundamental questions remain concerning the TTF cascade initiation, progression, and termination. It is also not known why temporal progression only happens in neuroblasts but not in their differentiated progeny. In this work, we performed single-cell RNA sequencing of Drosophila medulla neuroblasts of all ages to study the temporal patterning process with single-cell resolution. Our scRNA-seq data revealed that sets of genes involved in different biological processes show high to low or low to high gradients as neuroblasts age. We also identified a list of novel TTFs, and experimentally characterized their roles in the temporal progression and neural fate specification. Our study revealed a comprehensive temporal gene network that patterns medulla neuroblasts from start to end. Furthermore, we found that the progression and termination of this temporal cascade also require transcription factors differentially expressed along the differentiation axis (neuroblasts -> -> neurons). Lola proteins function as a speed modulator of temporal progression in neuroblasts; while Nerfin-1, a factor required to suppress de-differentiation in post-mitotic neurons, acts at the final temporal stage together with the last TTF of the cascade, to promote the switch to gliogenesis and the cell cycle exit. Our comprehensive study of the medulla neuroblast temporal cascade illustrated mechanisms that might be conserved in the temporal patterning of neural stem cells.
2021-12-27 | GSE168553 | GEO
Project description:Temporal patterning is an important mechanism for generating a great diversity of neuron subtypes from a seemingly homogenous progenitor pool in both vertebrates and invertebrates. Drosophila neuroblasts are temporally patterned by sequentially expressed Temporal Transcription Factors (TTFs). These TTFs are proposed to form a transcriptional cascade based on mutant phenotypes, although direct transcriptional regulation between TTFs has not been verified in most cases. Furthermore, it is not known how the temporal transitions are coupled with the generation of the appropriate number of neurons at each stage. We use neuroblasts of the Drosophila optic lobe medulla to address these questions and show that the expression of TTFs Sloppy-paired 1/2 (Slp1/2) is directly regulated at the transcriptional level by two other TTFs and the cell-cycle dependent Notch signaling through two cis-regulatory elements. We also show that supplying constitutively active Notch can rescue the delayed transition into the Slp stage in cell cycle arrested neuroblasts. Our findings reveal a novel Notch-pathway dependent mechanism through which the cell cycle progression regulates the timing of a temporal transition within a TTF transcriptional cascade.
| S-EPMC9427115 | biostudies-literature
Project description:Notch signaling is a core patterning module for vascular morphogenesis, which co-determines the sprouting behaviour of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability, and diminished Notch-induced target gene expression in ECs. In mice, loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase, which fine-tunes endothelial Notch responses during angiogenic sprouting.
2019-04-11 | PXD013192 | Pride
Project description:A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing
| PRJNA708282 | ENA
Project description:In the developing neocortex, a diverse array of neurons with defined types and abundances are systematically generated by a limited population of radial glial progenitors (RGPs) as they undergo successive fate changes. How this temporal patterning is regulated at the molecular level remains largely unknown. Here we present an in-depth single-cell multi-omics assay for deep characterization of regulatory programs, along with an analytical framework that integrates joint dynamics in single-cell transcription and chromatin structure to interrogate the regulation of temporal identities and fate progression of RGPs. We found that RGP temporal patterning is governed by a two-layered regulatory structure consisting of global regulators acting upon a cascade of transcription factor (TF) hubs. This cascade proceeds not by confining cascaded TF expression to specific temporal windows, but through synergistic transcriptional and epigenetic dynamics that temporally modulate TF regulatory activity. Furthermore, global regulators exhibit a progressively increasing expression pattern, and our computational modeling analysis found that the gradient of this pattern specifies the duration of each cascading stage and, subsequently, the abundance of specific progeny output. Together, this two-layered regulatory structure offers a mechanistic control of temporal patterning and emphasizes the importance of global regulators in managing temporal programs.
2025-05-23 | GSE204701 | GEO
Project description:Notch signalling is involved in a multitude of developmental decisions and its aberrant activation is linked to many diseases, including cancers. One such example is the neural stem cell tumours that arise from constitutive Notch activity in Drosophila neuroblasts. To investigate how hyper-activation of Notch in larval neuroblasts leads to tumours, we combined results from profiling the upregulated mRNAs and mapping the regions bound by Su(H) (the core Notch pathway transcription factor ). This identified 127 putative direct Notch targets that were up-regulated in the hyperplastic tissue. These genes were highly enriched for transcription factors (TFs) and overlapped significantly with a previously identified regulatory programme dependent on the proneural transcription factor Asense. Included were genes associated with the neuroblast maintenance and self-renewal programme that we validated as Notch regulated in vivo. A second category contained so-called temporal transcription factors, which are involved in neuroblast progression. Normally expressed in specific time windows, several temporal transcription factors were ectopically expressed in the stem cell tumours, suggesting that Notch had reprogrammed the normal temporal hierarchy. Indeed, the Notch-induced hyperplasia was reduced by mutations affecting two of the temporal factors which, conversely, were sufficient to induce mild hyperplasia on their own. Altogether the results demonstrate that Notch induces neural stem cell tumors by promoting the expression of genes that contribute to stem cell identity and by reprogramming expression of temporal factors that regulate maturity.
2016-10-18 | E-MTAB-3561 | biostudies-arrayexpress
Project description:Spatial patterning of neural stem cell populations is a powerful mechanism by which to generate neuronal diversity. In the developing Drosophila medulla, the symmetrically dividing stem cells of the outer proliferation center (OPC) crescent are spatially patterned by the non-overlapping expression of three transcription factors: Vsx1 in the center, Optix in the adjacent arms and Rx in the tips. These spatial genes compartmentalize the OPC and, together with the temporal patterning of the neuroblasts derived from the OPC, act to diversify medulla neuronal fates. The observation that the dorsal and ventral halves of the OPC grow as distinct compartments, together with the fact that a subset of neuronal types are generated from only one half of the crescent, suggests that additional transcription factors spatially pattern the OPC along the D-V axis. Here, we identify the spalt (salm and salr) and disco (disco and disco-r) genes as the D-V patterning transcription factors of the OPC. Spalt and Disco are differentially expressed in the dorsal and ventral OPC from the embryo through to the third instar larva, where they cross-repress each other to form a sharp dorsal-ventral boundary. We show that hedgehog is necessary for disco expression in the embryonic optic placode and that disco is subsequently required for the development of the ventral OPC and its neuronal progeny. We further demonstrate that this D-V patterning axis acts independently of Vsx1-Optix-Rx and thus propose that Spalt and Disco represent a third OPC patterning axis that may act to further diversify medulla fates.
2022-09-19 | GSE205934 | GEO
Project description:Neural cell type diversity arises from both spatial and temporal patterning of neural stem cells. Although spatial patterning mechanisms have been extensively studied, temporal patterning mechanisms remain relatively unexplored. In this study, we addressed generation of diverse neural cell types through lineage progression of mouse cortical radial glia. The time series scRNA-seq and snATAC-seq of mouse cortical development revealed that radial glia temporally transitioned from neurogenesis to gliogenesis. During gliogenic stages, various cell types were generated simultaneously along multidirectional lineage trajectories. We established comprehensive molecular maps for cortical lineage commitment and cellular diversification. The transcriptome and epigenome of cortical radial glia exhibit temporal dynamics, as revealed by scRNA-seq and snATAC-seq. Lhx2, a transcription factor with temporal dynamic chromatin binding activities, was identified as a key regulator of the neurogenesis-to-gliogenesis transition. It maintains neurogenic competence by establishing the active epigenetic state of its target genes.
2025-06-05 | GSE298892 | GEO
Project description:Neural cell type diversity arises from both spatial and temporal patterning of neural stem cells. Although spatial patterning mechanisms have been extensively studied, temporal patterning mechanisms remain relatively unexplored. In this study, we addressed generation of diverse neural cell types through lineage progression of mouse cortical radial glia. The time series scRNA-seq and snATAC-seq of mouse cortical development revealed that radial glia temporally transitioned from neurogenesis to gliogenesis. During gliogenic stages, various cell types were generated simultaneously along multidirectional lineage trajectories. We established comprehensive molecular maps for cortical lineage commitment and cellular diversification. The transcriptome and epigenome of cortical radial glia exhibit temporal dynamics, as revealed by scRNA-seq and snATAC-seq. Lhx2, a transcription factor with temporal dynamic chromatin binding activities, was identified as a key regulator of the neurogenesis-to-gliogenesis transition. It maintains neurogenic competence by establishing the active epigenetic state of its target genes.
2024-09-03 | GSE276209 | GEO