Modelling co-development between the somites and neural tube in human trunk-like structures

Nat Cell Biol. 2025 Dec;27(12):2049-2062. doi: 10.1038/s41556-025-01813-8. Epub 2025 Dec 16.

Abstract

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.

MeSH terms

  • Aldehyde Dehydrogenase 1 Family / genetics
  • Aldehyde Dehydrogenase 1 Family / metabolism
  • Body Patterning*
  • Cell Differentiation
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Models, Biological
  • Neural Tube* / embryology
  • Neural Tube* / metabolism
  • Notochord / embryology
  • Notochord / metabolism
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • Signal Transduction
  • Somites* / cytology
  • Somites* / embryology
  • Somites* / metabolism
  • Torso* / embryology
  • Tretinoin / metabolism

Substances

  • Hedgehog Proteins
  • Tretinoin
  • Aldehyde Dehydrogenase 1 Family
  • Retinal Dehydrogenase
  • SHH protein, human