A Notch-dependent transcriptional mechanism controls expression of temporal patterning factors in <i>Drosophila</i> medulla

Ray, Alokananda; Li, Xin

doi:10.1101/2021.10.29.466469

Cited by 3 publications

(5 citation statements)

References 113 publications

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“…N activation phenocopied loss of Nerfin‐1, resulting in neuron to NB dedifferentiation (Vissers et al , 2018 ; Fig 8A–E ). Furthermore, it was recently shown that the N pathway regulates Slp1 and Slp2 expression in medulla NBs through direct binding to Slp1/2 enhancers (preprint: Ray & Li, 2021 ). To test whether N activation, such as Dpn overexpression, stalled tTF progression, we assessed Slp expression in medulla regions where UAS‐N ACT was expressed under the control of eyR16F10‐GAL4 .…”

Section: Resultsmentioning

confidence: 99%

Dedifferentiation‐derived neural stem cells exhibit perturbed temporal progression

et al. 2023

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Dedifferentiation is the reversion of mature cells to a stem cell‐like fate, whereby gene expression programs are altered and genes associated with multipotency are (re)expressed. Misexpression of multipotency factors and pathways causes the formation of ectopic neural stem cells (NSCs). Whether dedifferentiated NSCs faithfully produce the correct number and types of progeny, or undergo timely terminal differentiation, has not been assessed. Here, we show that ectopic NSCs induced via bHLH transcription factor Deadpan (Dpn) expression fail to undergo appropriate temporal progression by constantly expressing mid‐temporal transcription factor(tTF), Sloppy‐paired 1/2 (Slp). Consequently, this resulted in impaired terminal differenation and generated an excess of Twin of eyeless (Toy)‐positive neurons at the expense of Reversed polarity (Repo)‐positive glial cells. Preference for a mid‐temporal fate in these ectopic NSCs is concordant with an enriched binding of Dpn at mid‐tTF loci and a depletion of Dpn binding at early‐ and late‐tTF loci. Retriggering the temporal series via manipulation of the temporal series or cell cycle is sufficient to reinstate neuronal diversity and timely termination.

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Section: Resultsmentioning

confidence: 99%

Dedifferentiation‐derived neural stem cells exhibit perturbed temporal progression

et al. 2023

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“…We have previously identified Notch (N) to be a Nerfin-1 target gene, where N activation phenocopied loss of Nerfin-1, resulting in neuron to NB dedifferentiation (Vissers et al, 2018) (Figure 6 A-E). Recently, it was shown that the N pathway regulates Slp1 and Slp2 expression in medulla NBs through direct binding to Slp1/2 enhancers (Ray and Li, 2021). To test whether similar to Dpn overexpression, N activation also stalled tTF progression, we assessed Slp expression in medulla regions where UAS-N ACT was expressed under the control of eyR16F10-GAL4 .…”

Section: Resultsmentioning

confidence: 99%

“…Recently, it was shown that the N pathway regulates Slp1 and Slp2 expression in medulla 9 NBs through direct binding to Slp1/2 enhancers (Ray and Li, 2021). To test whether similar to Dpn overexpression, N activation also stalled tTF progression, we assessed Slp expression in medulla regions where UAS-N ACT was expressed under the control of eyR16F10-GAL4.…”

Section: Notch-mediated Dedifferentiation Also Causes Temporal Series...mentioning

confidence: 99%

Cell cycle and temporal transcription factors regulate proliferation and neuronal diversity of dedifferentiation-derived neural stem cells

Cheng

Veen

Froldi

et al. 2022

Preprint

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Dedifferentiation is the reversion of differentiated cells to a stem cell like fate, whereby, the gene expression program of mature cells is altered and genes associated with multipotency are expressed. Appropriate terminal differentiation of NSCs is essential for restricting the overall number of neurons produced; in addition, faithful production of neuronal subtypes that populate the brain is important for NSC function. Both characteristics of NSCs are specified through temporal patterning of the NSCs driven by the successive expression of temporal transcription factors (tTFs). In this study, we found that ectopic NSCs induced via bHLH transcription factor Deadpan (Dpn) expression fail to undergo timely expression of temporal transcription factors (tTFs), where they express mid-tTF, Sloppy-paired 1 (Slp-1) and fail to express late-tTF Tailless (Tll); consequently generating an excess of Twin of eyeless (Toy) positive neurons at the expense of Reversed polarity (Repo) positive glial cells. In addition to disrupted production of neuronal/glial progeny, Dpn overexpression also resulted in stalled progression through the cell cycle, and a failure to undergo timely terminal differentiation. Mechanistically, DamID studies demonstrated that Dpn directly binds to both Dichaete (D), a Sox-box transcription factor known to repress Slp-1, as well as a number of cell cycle genes. Promoting cell cycle progression or overexpression of D were able to re-trigger the progression of the temporal series in dedifferentiated NBs, restoring both neuronal diversity and timely NB terminal differentiation.

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“…Interestingly, the second peak of Notch activation coincides with Klu expression and upregulates its expression ( Figure 2b ) [ 62 ]. Similarly, Notch signalling controls the expression of Slp in medulla NBs [ 50 ]. The temporal dynamics of Notch signal activity may control the temporal regulation of neurogenesis in other developmental contexts.…”

Section: Temporal Patterning Following the Proneural Wave In The Larv...mentioning

confidence: 99%

“…They promote the transition from Ey- to Slp-positive NBs [ 27 , 29 ]. These TTFs have been identified as target genes of Ey by TaDa analysis using the Ey-Dam fusion protein [ 50 ].…”

Section: Temporal Patterning Following the Proneural Wave In The Larv...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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A Notch-dependent transcriptional mechanism controls expression of temporal patterning factors in Drosophila medulla

Cited by 3 publications

References 113 publications

Dedifferentiation‐derived neural stem cells exhibit perturbed temporal progression

Dedifferentiation‐derived neural stem cells exhibit perturbed temporal progression

Cell cycle and temporal transcription factors regulate proliferation and neuronal diversity of dedifferentiation-derived neural stem cells

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

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