Spatial distribution and characterization of non-apical progenitors in the zebrafish embryo central nervous system

McIntosh, Rebecca; Norris, Joseph M.; Clarke, Jon; Alexandre, Paula

doi:10.1098/rsob.160312

Cited by 27 publications

(22 citation statements)

References 42 publications

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“…These observations show spinal neurons and NAPs share common stereotypical morphological behaviours, and further confirm that spinal Vsx1 NAPs and differentiating neurons share cellular and molecular characteristics as suggested previously (McIntosh et al, 2017).…”

Section: Non-apical Progenitors In Spinal Cord Also Extend Basal Protsupporting

confidence: 90%

“…In addition to the apical progenitors that generate most of the neurons of zebrafish CNS, a scarce population of basal progenitors that divide in non-apical locations is also present (Alexandre et al, 2010, McIntosh et al, 2017. We call these progenitors, Non-Apical Progenitors (or NAPs) and previously demonstrated that the majority of spinal NAPs express Vsx1 and share molecular and regulatory mechanisms with neurons (McIntosh et al, 2017). This prompted us to investigate whether spinal NAPs might also share the morphological programme of differentiation with neurons.…”

Section: Non-apical Progenitors In Spinal Cord Also Extend Basal Protmentioning

confidence: 99%

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Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

Hadjivasiliou

Moore

McIntosh

et al. 2019

Preprint

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During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.

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Section: Non-apical Progenitors In Spinal Cord Also Extend Basal Protsupporting

confidence: 90%

Section: Non-apical Progenitors In Spinal Cord Also Extend Basal Protmentioning

confidence: 99%

Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

Hadjivasiliou

Moore

McIntosh

et al. 2019

Preprint

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“…4H; Table S2.3), defining this domain as V2 interneurons. vsx1expressing cells in the hindbrain and spinal cord have been defined as non-apical progenitors, able to generate one excitatory (V2a) and one inhibitory (V2b) interneuron, and have been proposed to be a pool important for rapid generation of the sensory-locomotor circuit (McIntosh et al, 2017); their molecular signature is reported in Fig. 4D.…”

Section: Characterisation Of Neuronal Complexitymentioning

confidence: 99%

A single cell transcriptome atlas of the developing zebrafish hindbrain

2020

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Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at boundaries and segment centres, in part mediated by Fgf20 signalling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.

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“…Fig.4). vsx1-expressing cells in the hindbrain and spinal cord have been defined as non-apical progenitors, able to generate one excitatory (V2a) and one inhibitory (V2b) interneuron, and proposed to be a pool important for rapid generation of the sensory-locomotor circuit (McIntosh et al, 2017); their molecular signature is reported in Fig.4D. Motor neurons can be identified in C8 (isl1, isl2, phox2a), and in the hindbrain lhx4, nkx6.1 and tbx3a are expressed in these cells (Fig.4D).…”

Section: Resultsmentioning

confidence: 99%

A single cell transcriptome atlas of the developing zebrafish hindbrain

Tambalo

Mitter

Wilkinson

2019

Preprint

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Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at bounderies and segment centres, in part mediated by Fgf20 signaling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.

show abstract

Spatial distribution and characterization of non-apical progenitors in the zebrafish embryo central nervous system

Cited by 27 publications

References 42 publications

Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

A single cell transcriptome atlas of the developing zebrafish hindbrain

A single cell transcriptome atlas of the developing zebrafish hindbrain

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