Temporal cell fate determination in the spinal cord is mediated by the duration of Notch signalling

Jacobs, Craig T; Kejriwal, Aarti; Kocha, Katrinka M.; Jin, Kevin Y; Huang, Peng

doi:10.1016/j.ydbio.2022.05.010

Cited by 11 publications

(26 citation statements)

References 60 publications

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“…V2s neurons arise later than the initial wave of V2a/b pairs ( Gerber et al, 2019 ). Because Notch has been shown to exhibit different effects on cellular identity during early and late development, we suggest that delayed Notch activity causes some later born vsx1 + sister neurons to adopt a V2b/s identity, which are both Notch ON ( Jacobs et al, 2022 ). Similarly, only early cerebellar progenitors appear to undergo Notch differentiation into distinct cell types, the Purkinje and granule cells ( Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 95%

Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits

Bello-Rojas

Bagnall

2022

eLife

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Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In Drosophila, in contrast, sister neurons with different levels of Notch expression (NotchON/NotchOFF) develop distinct identities and diverge into separate circuits. Notch-differentiated sister neurons have been observed in vertebrate spinal cord and cerebellum, but whether they integrate into shared or distinct circuits remains unknown. Here, we evaluate how sister V2a (NotchOFF)/V2b (NotchON) neurons in the zebrafish integrate into spinal circuits. Using an in vivo labeling approach, we identified pairs of sister V2a/b neurons born from individual Vsx1+ progenitors and observed that they have somata in close proximity to each other and similar axonal trajectories. However, paired whole-cell electrophysiology and optogenetics revealed that sister V2a/b neurons receive input from distinct presynaptic sources, do not communicate with each other, and connect to largely distinct targets. These results resemble the divergent connectivity in Drosophila and represent the first evidence of Notch-differentiated circuit integration in a vertebrate system.

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Section: Discussionmentioning

confidence: 95%

Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits

Bello-Rojas

Bagnall

2022

eLife

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“…Previous cell lineage tracing and genetic data indicated that LFP progenitor cells give rise to KA” and V3 interneurons in a sequential manner (Huang et al, 2012; Jacobs and Huang, 2019; Jacobs et al, 2022; Yang et al, 2010). In this sequence of events, KA” cells are the first to be generated at about 16 hpf (hours post fertilization), followed by V3 cells at approximately 24 hpf.…”

Section: Resultsmentioning

confidence: 99%

“…LFP cells with high Notch signalling do not differentiate and remain in a progenitor state. Inhibition of this pathway leads to the differentiation of progenitors into interneurons (Huang et al, 2012; Jacobs and Huang, 2019; Jacobs et al, 2022). Since ISNs are located ventrally in the spinal cord, the precursors of these neurons share the expression of several transcription factor genes with LFP cells such as foxa, nkx2 .…”

Section: Resultsmentioning

confidence: 99%

“…Recent work has indicated that LFP progenitors generate first KA” interneurons and later V3 interneurons (Jacobs et al, 2022). Our results suggest that ISNs, which are generated even later than V3 neurons, also develop from LFPs.…”

Section: Resultsmentioning

confidence: 99%

“…These cells also express genes involved in cell cycles such as mki67, mcm5 and mcm2 (Table S2). In addition, these cells strongly express genes involved in Notch signal reception and processing such as notch3 receptor and downstream targets like her12, her2, her9, her6, her8a and her4 (Table S 2).Differentiation of KA” and V3 interneurons from LFP progenitors has been shown to require downregulation of Notch signalling (Jacobs and Huang, 2019; Jacobs et al, 2022). Thus, we asked whether the development of ISNs from LFP cells also depends on the down-regulation of this pathway.…”

Section: Resultsmentioning

confidence: 99%

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Temporal single-cell transcriptomic analysis of thesox1a:eGFPtransgenic line identified the lateral floor plate progenitor cells as the origin of intraspinal serotonergic neurons

Chen

Köhler

Cucun

et al. 2023

Preprint

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The Sox family of transcription factors plays a crucial role in the development of the vertebrate nervous system. In the zebrafish embryo,sox1genes are expressed in neural progenitor cells and neurons of the ventral spinal cord. We recently reported that the loss of function ofsox1aandsox1bleads to a significant decline in a subtype of V2 neurons, called V2s, in zebrafish. Here, a single-cell RNA sequencing approach was used to analyse the transcriptome ofsox1alineage progenitors and neurons in the zebrafish spinal cord at four different time points during the first five days of embryonic development, using the Tg(sox1a:eGFP) line. In addition to the previously describedsox1a-expressing neurons, we found thatsox1ais also expressed in late-developing intraspinal serotonergic neurons (ISNs). Analysis of developmental trajectories from single-cell data and depletion of lateral floor plate (LFP) cells bynkx2.9morpholino knockdown suggest that ISNs arise from LFP precursor cells. Pharmacological inhibition of the Notch signalling pathway indicates that this pathway is required for the negative regulation of the development of LFP progenitor cells into ISN populations. Our results show that the zebrafish LFP is a precursor domain that longitudinally gives rise to ISNs in addition to the previously described KA” and V3 interneurons.

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sox1a:eGFP transgenic line and single-cell transcriptomics reveal the origin of zebrafish intraspinal serotonergic neurons

Chen¹,

Köhler²,

Cucun³

et al. 2023

iScience

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Temporal cell fate determination in the spinal cord is mediated by the duration of Notch signalling

Cited by 11 publications

References 60 publications

Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits

Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits

Temporal single-cell transcriptomic analysis of thesox1a:eGFPtransgenic line identified the lateral floor plate progenitor cells as the origin of intraspinal serotonergic neurons

sox1a:eGFP transgenic line and single-cell transcriptomics reveal the origin of zebrafish intraspinal serotonergic neurons

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