Co-development of central and peripheral neurons with trunk mesendoderm in human elongating multi-lineage organized gastruloids

Nat Commun. 2021 May 21;12(1):3020. doi: 10.1038/s41467-021-23294-7.

Abstract

Stem cell technologies including self-assembling 3D tissue models provide access to early human neurodevelopment and fundamental insights into neuropathologies. Gastruloid models have not been used to investigate co-developing central and peripheral neuronal systems with trunk mesendoderm which we achieve here in elongating multi-lineage organized (EMLO) gastruloids. We evaluate EMLOs over a forty-day period, applying immunofluorescence of multi-lineage and functional biomarkers, including day 16 single-cell RNA-Seq, and evaluation of ectodermal and non-ectodermal neural crest cells (NCCs). We identify NCCs that differentiate to form peripheral neurons integrated with an upstream spinal cord region after day 8. This follows initial EMLO polarization events that coordinate with endoderm differentiation and primitive gut tube formation during multicellular spatial reorganization. This combined human central-peripheral nervous system model of early organogenesis highlights developmental events of mesendoderm and neuromuscular trunk regions and enables systemic studies of tissue interactions and innervation of neuromuscular, enteric and cardiac relevance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers
  • Cell Differentiation / physiology
  • Central Nervous System / cytology*
  • Central Nervous System / physiology*
  • Forkhead Transcription Factors
  • Gene Expression
  • Humans
  • Morphogenesis
  • Neural Crest
  • Peripheral Nervous System / cytology*
  • Peripheral Nervous System / pathology*
  • Phenotype
  • SOXE Transcription Factors
  • Transcription Factor AP-2

Substances

  • Biomarkers
  • FOXD3 protein, human
  • Forkhead Transcription Factors
  • SOX10 protein, human
  • SOXE Transcription Factors
  • TFAP2A protein, human
  • Transcription Factor AP-2