Modelling co-development between the somites and neural tube in human trunk-like structures
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Komal Makwana Louise Tilley Probir Chakravarty Jamie Thompson Peter Baillie-Benson Ignacio Rodriguez Naomi MorisAbstract
Human stem cell-based embryo models provide experimentally amenable in vitro systems for developmental research. A key feature of embryo models is their multi-lineage differentiation, which allows for the study of tissue co-development. Here we develop human trunk-like structures that have morphologically organized somites and a neural tube that form through self-organized, endogenous signalling. Transcriptomic comparison with human embryo datasets suggests that human trunk-like structure cells approximate Carnegie stage 13-14 (28-35 days after fertilization). The absence of a notochord leads to a dorsal identity, but exogenous Sonic Hedgehog signalling activation ventralizes both the somites and the neural tube in a dose-dependent manner. We further identify reciprocal signalling: neural tube-derived cues induce medial ALDH1A2 in somites, which in turn generate retinoic acid signals that drive spontaneous neural-tube patterning. Together, our data highlight the value of modularity in embryo models, which we leverage to explore human trunk co-development.
Journal details
Journal
Nature Cell Biology
Volume
27
Issue number
12
Pages
2049-2062
Available online
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10.1038/s41556-025-01813-8
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Europe PubMed Central
41402467
Pubmed
41402467
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The publication was previously a preprint.
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