Developmental cell fate choice in neural tube progenitors employs two distinct cis-regulatory strategies

Delás, M. Joaquina; Kalaitzis, Christos M; Fawzi, Tamara; Demuth, Madeleine; Zhang, Isabel; Stuart, Hannah; Costantini, Elena; Ivanovitch, Kenzo; Tanaka, Elly M.; Briscoe, James

doi:10.1016/j.devcel.2022.11.016

Cited by 23 publications

(26 citation statements)

References 91 publications

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“…These are expressed in neural progenitors along the entire dorsal ventral axis (Fig 1A). To understand how spinal cord progenitors integrate their dorsoventral spatial identity with the temporal progression of cell fate changes, we made use of an in vitro cellular model of spinal cord development based on the directed differentiation of embryonic stem cells (ESCs) (Delás et al, 2023; Gouti et al, 2014) (Fig 1B). We assayed in vitro generated ventral neural progenitors (NPs) from day 5 until day 11 of differentiation.…”

Section: Resultsmentioning

confidence: 99%

“…Cryosectioning (14 μm sections) was performed on a Cryostat LEICA CM3050S using SuperFrost slides (Thermo Fisher, 10149870). Immunostaining was performed as previously described (Delás et al, 2023), using the following antibodies. Mouse: mouse anti-NKX6.1 (1:100, DSHB, F55A10), rabbit anti-NFIA (1:1000, Atlas Antibodies, HPA008884), goat anti-OLIG2 (1:500, R&D Systems, AF2418).…”

Section: Immunohistochemistry Of Embryo Sectionsmentioning

confidence: 99%

“…CaTS-ATAC-seq (Crosslinked and TF-Sorted ATACseq) CaTS-ATAC was performed as previously described (Delás et al, 2023) with in-house produced Tn5. A dead cell removal step was introduced to enrich for live cells prior to fixation and transposition.…”

Section: Rna Extraction and Rt-qpcrmentioning

confidence: 99%

“…A set of cis-regulatory elements (CREs) responsible for directing gene expression in neural progenitors has been identified (Delás et al, 2023; Kutejova et al, 2016; Nishi et al, 2015; Oosterveen et al, 2012; Peterson et al, 2012). By contrast to Drosophila , most neural progenitors share a common chromatin landscape, with minimal variation in the accessibility of CREs across progenitor types, at the early stages of neural tube patterning, despite the significant functional and gene expression differences.…”

Section: Introductionmentioning

confidence: 99%

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The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

Zhang,

Boezio,

Cornwall-Scoones

et al. 2024

Preprint

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The vertebrate neural tube generates a large diversity of molecularly and functionally distinct neurons and glia from a small progenitor pool. While the role of spatial patterning in organising cell fate specification has been extensively studied, temporal patterning, which controls the timing of cell type generation, is equally important. Here we define a global temporal programme in the spinal cord. This governs cell fate choices by regulating chromatin accessibility in neural progenitors. Perturbation of this cis-regulatory programme affects sequential transitions in spinal cord progenitors and the identity of progeny. The temporal programme operates in parallel to spatial patterning, ensuring the timely availability of regulatory elements for spatial determinants to direct cell-type specific gene expression. These findings identify a chronotopic spatiotemporal integration strategy in which a global temporal chromatin programme determines the output of a spatial gene regulatory network resulting in the temporally and spatially ordered allocation of cell type identity.

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Section: Resultsmentioning

confidence: 99%

Section: Immunohistochemistry Of Embryo Sectionsmentioning

confidence: 99%

Section: Rna Extraction and Rt-qpcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

Zhang,

Boezio,

Cornwall-Scoones

et al. 2024

Preprint

Self Cite

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“…Delas et al 2023 (Delás et al, 2023) propose two cis -regulatory strategies that could drive cell fate choice in developing neural progenitors: One - differential binding - relies on a common regulatory landscape, whereby the different composition of TFs at these cis -regulatory elements dictates differential gene expression and cell fate decisions. The other - differential accessibility - relies on cell-type-specific chromatin remodeling.…”

Section: Discussionmentioning

confidence: 99%

Spatial enhancer activation determines inhibitory neuron identity

Dvoretskova

Kittke

et al. 2023

Preprint

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The mammalian telencephalon contains a tremendous diversity of GABAergic projection neuron and interneuron types, that originate in a germinal zone of the embryonic basal ganglia. How genetic information in this transient structure is transformed into different cell types is not yet fully understood. Using a combination ofin vivolineage tracing, CRISPR perturbation and ChIP-seq in mice, we found that the transcription factor MEIS2 favors the development of projection neurons through genomic binding sites in regulatory enhancers of projection neuron specific genes. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity towards these sites. In interneurons, the activation of projection neuron specific enhancers by MEIS2 and DLX5 is repressed by the transcription factor LHX6. When MEIS2 carries a mutation associated with intellectual disability in humans, it is less effective at activating enhancers involved in projection neuron development. This suggests that GABAergic differentiation may be impaired in patients carrying this mutation. Our research has uncovered a mechanism by which the selective activation of enhancers plays a crucial role in the establishment of neuronal identity, as well as in potential pathological mechanisms.

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