Drosophila Neuroblast Selection Is Gated by Notch, Snail, SoxB, and EMT Gene Interplay

Arefin, Badrul; Parvin, Farjana; Bahrampour, Shahrzad; Stadler, Caroline Bivik; Thor, Stefan

doi:10.1016/j.celrep.2019.11.038

Cited by 20 publications

(23 citation statements)

References 109 publications

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“…SoxN is a SoxB family HMG-domain transcription factor involved in neuroblast formation and neuron differentiation in the ventral nerve cord [52][53][54][55] . Its expression has been noted in the medulla 19 , but its function in the medulla has not been studied.…”

Section: Soxn and Dmrt99b Cooperate With Hth To Specify The First Temporal Identitymentioning

confidence: 99%

A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing

Zhu

et al. 2021

Preprint

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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 approaches 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.

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Section: Soxn and Dmrt99b Cooperate With Hth To Specify The First Temporal Identitymentioning

confidence: 99%

A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing

Zhu

et al. 2021

Preprint

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“…Their broad neuroectodermal expression and the continued cell divisions in the expression domains are in line with the evolutionary conserved role of SoxB TFs in the GRN conferring neurogenic potential to ectodermal cells (Hartenstein & Stollewerk, 2015). Beyond this, the timing of expression may also conform with an involvement in NB formation and specification and subsequent neural differentiation, as demonstrated for SoxNeuro and Dichaete in D. melanogaster (Aleksic et al, 2013;Arefin et al, 2019;Buescher et al, 2002;Ferrero et al, 2014;Overton et al, 2002;Zhao & Skeath, 2002;Zhao et al, 2007). In P. virginalis, the specific roles of the different SoxB TFs during neurogenesis still need to be further elucidated with functional data.…”

Section: Soxb Group Tfs In the Developing Cns Of P Virginalismentioning

confidence: 57%

Insights into the genetic regulatory network underlying neurogenesis in the parthenogenetic marbled crayfish Procambarus virginalis

Brenneis

Schwentner

Giribet

et al. 2021

Developmental Neurobiology

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Nervous system development has been intensely studied in insects (especially Drosophila melanogaster), providing detailed insights into the genetic regulatory network governing the formation and maintenance of the neural stem cells (neuroblasts) and the differentiation of their progeny. Despite notable advances over the last two decades, neurogenesis in other arthropod groups remains by comparison less well understood, hampering finer resolution of evolutionary cell type transformations and changes in the genetic regulatory network in some branches of the arthropod tree of life. Although the neurogenic cellular machinery in malacostracan crustaceans is well described morphologically, its genetic molecular characterization is pending. To address this, we established an in situ hybridization protocol for the crayfish Procambarus virginalis and studied embryonic expression patterns of a suite of key genes, encompassing three SoxB group transcription factors, two achaete-scute homologs, a Snail family member, the differentiation determinants Prospero and Brain tumor, and the neuron marker Elav. We document cell type expression patterns with notable similarities to insects and branchiopod crustaceans, lending further support to the homology of hexapod-crustacean neuroblasts and their cell lineages. Remarkably, in the crayfish head region, cell emigration from the neuroectoderm coupled with gene expression data points to a neuroblast-independent initial phase of brain neurogenesis. Further, SoxB group expression patterns suggest an involvement of Dichaete in segmentation, in concordance with insects. Our target gene set is a promising starting point for further embryonic studies, as well as for the molecular genetic characterization of subregions and cell types in the neurogenic systems in the adult crayfish brain.

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“…By extension, NSC delamination in the embryonic neuroectoderm can be seen as a collective process involving both the delaminating cell and its ectodermal neighbors as delaminating NSCs signal to their neuroectodermal neighbors to remain epithelial. Whether and how Notch activation in neuroectodermal cells regulate in a feed-back manner NSC delamination remains to be studied Arefin et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Neuralized regulates a travelling wave of Epithelium-to-Neural Stem Cell morphogenesis inDrosophila

Shard

Luna-Escalante

Schweisguth

2020

Preprint

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Many tissues are produced during development by specialized progenitor cells emanating from epithelia via an Epithelial-to-Mesenchymal Transition (EMT). Most studies have so far focused on cases involving single or isolated groups of cells. Here we describe an EMT-like process that requires tissue level coordination. This EMT-like process occurs along a continuous front in the Drosophila optic lobe neuroepithelium to produce neural stem cells (NSCs). We find that emerging NSCs remain epithelial and apically constrict before dividing asymmetrically to produce neurons. Apical constriction is associated with contractile myosin pulses and requires the E3 ubiquitin ligase Neuralized and RhoGEF3. Neuralized downregulates the apical protein Crumbs via its interaction with Stardust. Disrupting the regulation of Crumbs by Neuralized led to defects in apical constriction and junctional myosin accumulation, and to imprecision in the integration of emerging NSCs into the transition front. Neuralized therefore appears to mechanically couple NSC fate acquisition with cell-cell rearrangement to promote smooth progression of the differentiation front. excitable reaction-diffusion mechanism. Accordingly, an activator signal, the Epidermal Growth Factor (EGF) Spitz, spreads in the NE by diffusion and self-induction and triggers a negative feed-back via the production of a non-diffusible inhibitor, i.e. the proneural factor Lethal of scute (L'sc) that inhibits the production of active Spitz by promoting NE-to-NSC

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Drosophila Neuroblast Selection Is Gated by Notch, Snail, SoxB, and EMT Gene Interplay

Cited by 20 publications

References 109 publications

A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing

A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing

Insights into the genetic regulatory network underlying neurogenesis in the parthenogenetic marbled crayfish Procambarus virginalis

Neuralized regulates a travelling wave of Epithelium-to-Neural Stem Cell morphogenesis inDrosophila

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