The molecular landscape of neural differentiation in the developing Drosophila brain revealed by targeted scRNA-seq and multi-informatic analysis

Michki, Nigel S; Li, Ye; Sanjasaz, Kayvon; Zhao, Yimeng; Shen, Fred Y.; Walker, Logan A.; Cao, Wenjia; Lee, Cheng-Yu; Cai, Dawen

doi:10.1016/j.celrep.2021.109039

Cited by 30 publications

(33 citation statements)

References 77 publications

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“…Fig. 2D), and we identified several other unique marker genes for each subtype (Ariss et al , 2020; Brunet Avalos et al , 2019; Cattenoz et al , 2016; Estacio-Gomez et al , 2020; Michki et al , 2021)(Suppl. Fig.…”

Section: Resultsmentioning

confidence: 87%

“…To determine clusters, marker genes of each cluster were identified by FindAllMarkers function (Seurat) and logistic regression analysis (Scanpy). Based on canonical markers and gene expression profiles, genes similar clusters were merged and annotated based on existing knowledge and literature (Ariss et al , 2020; Brunet Avalos et al , 2019; Cattenoz et al , 2016; Estacio-Gomez et al , 2020; Michki et al , 2021).…”

Section: Methodsmentioning

confidence: 99%

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Patient-associated mutations inDrosophilaAlk perturb neuronal differentiation and promote survival

Pfeifer

Wolfstetter

Anthonydhason

et al. 2022

Preprint

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Activating Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK) mutations occur in pediatric neuroblastoma, and are associated with poor prognosis. To study ALK-activating mutations in a genetically controllable system we employed CRIPSR/Cas9, incorporating orthologues of the human oncogenic mutations ALKF1174L and ALKY1278S in the Drosophila Alk locus. AlkF1251L and AlkY1355S mutant Drosophila exhibit enhanced Alk signaling phenotypes, but unexpectedly depend on the Jelly belly (Jeb) ligand for activation. Both AlkF1251L and AlkY1355S mutant larval brains display hyperplasia, represented by increased numbers of Alk-positive neurons. Despite this hyperplasic phenotype, no brain tumors were observed in mutant animals. We show that hyperplasia in Alk mutants was not caused by significantly increased rates of proliferation, but rather by decreased levels of apoptosis in the larval brain. Using single-cell RNA sequencing (scRNAseq), we have been able to identify perturbations during temporal fate specification in AlkY1355S mutant mushroom body lineages. These findings shed important light on the role of Alk in neurodevelopmental processes and highlight the potential of activating Alk mutations to perturb specification and promote survival in neuronal lineages.

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Section: Resultsmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Patient-associated mutations inDrosophilaAlk perturb neuronal differentiation and promote survival

Pfeifer

Wolfstetter

Anthonydhason

et al. 2022

Preprint

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show abstract

“…It is unclear whether the spatial organization and migration of radial glia during division—which are important in mammalian neurogenesis—are a conserved feature of Drosophila neurogenesis. However, recent studies have demonstrated that the neuroblast pool is highly heterogenous [ 85 , 86 , 87 ], hinting that spatial patterning may be more important in Drosophila than is currently understood. While tll can reprogram type I neuroblasts into type II neuroblasts, it is only successful in ≈60% of type I lineages [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Neural Stem Cell Competency and Commitment during Indirect Neurogenesis

Rajan

Ostgaard

Lee

2021

IJMS

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Indirect neurogenesis, during which neural stem cells generate neurons through intermediate progenitors, drives the evolution of lissencephalic brains to gyrencephalic brains. The mechanisms that specify intermediate progenitor identity and that regulate stem cell competency to generate intermediate progenitors remain poorly understood despite their roles in indirect neurogenesis. Well-characterized lineage hierarchy and available powerful genetic tools for manipulating gene functions make fruit fly neural stem cell (neuroblast) lineages an excellent in vivo paradigm for investigating the mechanisms that regulate neurogenesis. Type II neuroblasts in fly larval brains repeatedly undergo asymmetric divisions to generate intermediate neural progenitors (INPs) that undergo limited proliferation to increase the number of neurons generated per stem cell division. Here, we review key regulatory genes and the mechanisms by which they promote the specification and generation of INPs, safeguarding the indirect generation of neurons during fly larval brain neurogenesis. Homologs of these regulators of INPs have been shown to play important roles in regulating brain development in vertebrates. Insight into the precise regulation of intermediate progenitors will likely improve our understanding of the control of indirect neurogenesis during brain development and brain evolution.

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“…Compared with the embryonic CNS and OL, relatively fewer TTFs have been identified in Type II NBs in the CB. Type II NBs were specifically labelled and FACS sorted to perform Type II NB-specific scRNA-seq analyses [ 28 ]. The pseudotime analysis confirmed the temporal cascade of TTFs in INPs proposed in the previous genetic studies [ 19 , 20 ].…”

Section: Temporal Patterning Of Neuroblasts and Intermediate Progenit...mentioning

confidence: 99%

Cutting edge technologies expose the temporal regulation of neurogenesis in the Drosophila nervous system

Sato

Suzuki

2022

Fly

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During the development of the central nervous system (CNS), extremely large numbers of neurons are produced in a regular fashion to form precise neural circuits. During this process, neural progenitor cells produce different neurons over time due to their intrinsic gene regulatory mechanisms as well as extrinsic mechanisms. The Drosophila CNS has played an important role in elucidating the temporal mechanisms that control neurogenesis over time. It has been shown that a series of temporal transcription factors are sequentially expressed in neural progenitor cells and regulate the temporal specification of neurons in the embryonic CNS. Additionally, similar mechanisms are found in the developing optic lobe and central brain in the larval CNS. However, it is difficult to elucidate the function of numerous molecules in many different cell types solely by molecular genetic approaches. Recently, omics analysis using single-cell RNA-seq and other methods has been used to study the Drosophila nervous system on a large scale and is making a significant contribution to the understanding of the temporal mechanisms of neurogenesis. In this article, recent findings on the temporal patterning of neurogenesis and the contributions of cutting-edge technologies will be reviewed.

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The molecular landscape of neural differentiation in the developing Drosophila brain revealed by targeted scRNA-seq and multi-informatic analysis

Cited by 30 publications

References 77 publications

Patient-associated mutations inDrosophilaAlk perturb neuronal differentiation and promote survival

Patient-associated mutations inDrosophilaAlk perturb neuronal differentiation and promote survival

Regulation of Neural Stem Cell Competency and Commitment during Indirect Neurogenesis

Cutting edge technologies expose the temporal regulation of neurogenesis in the Drosophila nervous system

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