Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord

Shaker, Mohammed R.; Lee, Ju Hyun; Kim, Kyung Hyun; Ban, Saeli; Kim, Veronica Jihyun; Kim, Joo Yeon; Lee, Ji Yeoun; Sun, Woong

doi:10.1016/j.lfs.2021.119393

Cited by 17 publications

(9 citation statements)

References 57 publications

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“…‘Committed’ NC cells, located anteriorly at the same time points, were found to also express Sox9 alongside Tfap2a ( Figure 1 Ba-b and Be-f ). These data demonstrate that NC-fated axial progenitors in the mouse embryo exhibit T expression in line with the previous lineage tracing studies showing that T-positive embryonic cells contribute to the posterior neural tube and trunk NC ( Anderson et al, 2013 ; Mugele et al, 2018 ; Shaker et al, 2021 ).…”

Section: Resultssupporting

confidence: 91%

“…Fate mapping, lineage tracing, and single-cell transcriptomics studies in vertebrate embryos have revealed that trunk NC cells, which give rise to neuroblastoma (the most common extracranial solid tumour in infants) following oncogenic transformation, are derived from NMPs ( Javali et al, 2017 ; Lukoseviciute et al, 2021 ; Shaker et al, 2021 ; Tzouanacou et al, 2009 ; Wymeersch et al, 2016 ). Moreover, recent work has demonstrated that the in vitro generation of trunk NC cells and their derivatives from hPSCs relies on the induction of an NMP-like intermediate following stimulation of WNT/FGF signalling pathways ( Abu-Bonsrah et al, 2018 ; Faustino Martins et al, 2020 ; Frith et al, 2018 ; Frith and Tsakiridis, 2019 ; Hackland et al, 2019 ; Kirino et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor

Gogolou

Souilhol

Granata

et al. 2022

eLife

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The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive. Recent studies have indicated that trunk NC cells, the presumed precursors of the childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body (NMPs). Here we employ human embryonic stem cell differentiation to define how NMP-derived NC cells acquire a posterior axial identity. We show that TBXT, a pro-mesodermal transcription factor, mediates early posterior NC/spinal cord regionalisation together with WNT signalling effectors. This occurs by TBXT-driven chromatin remodelling via its binding in key enhancers within HOX gene clusters and other posterior regulator-associated loci. This initial posteriorisation event is succeeded by a second phase of trunk HOX gene control that marks the differentiation of NMPs toward their TBXT-negative NC/spinal cord derivatives and relies predominantly on FGF signalling. Our work reveals a previously unknown role of TBXT in influencing posterior NC fate and points to the existence of temporally discrete, cell type-dependent modes of posterior axial identity control.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor

Gogolou

Souilhol

Granata

et al. 2022

eLife

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“…The neural tube is the precursor of the brain and spinal cord and is derived from embryonic neural stem cells (NSCs) ( Pai et al, 2012 ). During early central nervous system (CNS) development, rostral and caudal NSCs are derived from distinct lineages, namely, neuroectoderm (NEct) and neuromesodermal progenitors (NMPs), respectively ( Shaker M. R. et al, 2021 ; Shaker et al, 2021c ; Hudson and Yasuo, 2021 ). These two distinct populations also differ in proliferation rates, differentiation potential, and ECM adhesion ( Shaker et al, 2015 ; Shaker M. R. et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Neural Epidermal Growth Factor-Like Like Protein 2 Is Expressed in Human Oligodendroglial Cell Types

Shaker

Kahtan

Prasad

et al. 2022

Front. Cell Dev. Biol.

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Neural epidermal growth factor-like like 2 (NELL2) is a cytoplasmic and secreted glycosylated protein with six epidermal growth factor-like domains. In animal models, NELL2 is predominantly expressed in neural tissues where it regulates neuronal differentiation, polarization, and axon guidance, but little is known about the role of NELL2 in human brain development. In this study, we show that rostral neural stem cells (rNSC) derived from human-induced pluripotent stem cell (hiPSC) exhibit particularly strong NELL2 expression and that NELL2 protein is enriched at the apical side of neural rosettes in hiPSC-derived brain organoids. Following differentiation of human rostral NSC into neurons, NELL2 remains robustly expressed but changes its subcellular localization from >20 small cytoplasmic foci in NSC to one–five large peri-nuclear puncta per neuron. Unexpectedly, we discovered that in human brain organoids, NELL2 is readily detectable in the oligodendroglia and that the number of NELL2 puncta increases as oligodendrocytes mature. Artificial intelligence-based machine learning further predicts a strong association of NELL2 with multiple human white matter diseases, suggesting that NELL2 may possess yet unexplored roles in regulating oligodendrogenesis and/or myelination during human cortical development and maturation.

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“…The copyright holder for this this version posted November 8, 2022. ; https://doi.org/10.1101/2022.11.07.515417 doi: bioRxiv preprint molecular players construct hindlimb motor pools. The discovery of neuromesodermal progenitors specialized for building the caudal part of the spinal cord indicates that the origin of caudal motor neurons is different from that of rostral motor neurons (Henrique, Abranches, Verrier, & Storey, 2015;Shaker et al, 2021). For instance, the fate mapping study of NMP populations revealed a rostral-to-caudal ascending gradient of motor neuron generation in the developing spinal cord, which indicated that a distinct genetic program guides lumbar motor pools separately (Shaker et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…The discovery of neuromesodermal progenitors specialized for building the caudal part of the spinal cord indicates that the origin of caudal motor neurons is different from that of rostral motor neurons (Henrique, Abranches, Verrier, & Storey, 2015; Shaker et al, 2021). For instance, the fate mapping study of NMP populations revealed a rostral-to-caudal ascending gradient of motor neuron generation in the developing spinal cord, which indicated that a distinct genetic program guides lumbar motor pools separately (Shaker et al, 2021). Additionally, some Hox genes, alongside their initial role in body patterning, are selectively expressed in motor neuron-lineage cells during the postmitotic stages and further define their caudal segmental identity.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2

Lee

Yeo

Kim

et al. 2022

Preprint

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The fidelity of motor control requires the precise positional arrangement of motor pools and the establishment of synaptic connections between these pools. In the developing spinal cord, motor nerves project to specific target muscles and receive proprioceptive input from the muscles via the sensorimotor circuit. LIM-homeodomain transcription factors are known to successively restrict specific motor neuronal fates during neural development; however, it remains unclear to what extent they contribute to limb-based motor pools and locomotor circuits. Here, we showed in mice that deletion of Isl2 resulted in scattered motor pools, primarily in the median motor column and lateral LMC (LMCl) populations, and lacked Pea3 expression in the hindlimb motor pools, accompanied by reduced terminal axon branching and disorganized neuromuscular junctions. Transcriptomic analysis of Isl2-deficient spinal cords revealed that a variety of genes involved in motor neuron differentiation, axon development, and synapse organization were downregulated in hindlimb motor pools. Moreover, the loss of Isl2 impaired sensorimotor connectivity and hindlimb locomotion. Together, our studies indicate that Isl2 plays a critical role in organizing motor pool position and sensorimotor circuits in hindlimb motor pools.

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Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord

Cited by 17 publications

References 57 publications

Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor

Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor

Neural Epidermal Growth Factor-Like Like Protein 2 Is Expressed in Human Oligodendroglial Cell Types

Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2

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