BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids
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Abstract
ABSTRACT Bone morphogenetic proteins (BMPs) are secreted regulators of cell fate in several developing tissues. In the embryonic spinal cord, they control the emergence of the neural crest, roof plate and distinct subsets of dorsal interneurons. Although a gradient of BMP activity has been proposed to determine cell type identity in vivo, whether this is sufficient for pattern formation in vitro is unclear. Here, we demonstrate that exposure to BMP4 initiates distinct spatial dynamics of BMP signalling within the self-emerging epithelia of both mouse and human pluripotent stem cell-derived spinal organoids. The pattern of BMP signalling results in the stereotyped spatial arrangement of dorsal neural tube cell types, and concentration, timing and duration of BMP4 exposure modulate these patterns. Moreover, differences in the duration of competence time-windows between mouse and human account for the species-specific tempo of neural differentiation. Together, this study describes efficient methods for generating patterned subsets of dorsal interneurons in spinal organoids and supports the conclusion that graded BMP activity orchestrates the spatial organization of the dorsal neural tube cellular diversity in mouse and human.
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The authors argue that this model surpasses earlier work that made separate motor-circuit components in 3D alone or in 2D co-culture.
“This represents a significant advance beyond prior models in which individual components of motor circuits have been generated in 3D in isolation or co-cultured in 2D (Duval et al., 2019; Ogura et al., 2018; Sances et al., 2016; Shi et al., 2018; Steinbeck et al., 2016).”
From Generation of Functional Human 3D Cortico-Motor Assembloids (2020) · cites this paper as Duval et al., 2019
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- Authors
- Duval, N., Vaslin, C., Barata, T. C., Frarma, Y., Contremoulins, V., Baudin, X., Nedelec, S., & Ribes, V. C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2019-07-15
- Volume
- 146
- Issue
- 14
- Pages
- dev175430
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2955408429
- Cited by
- 93
- References
- 56
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 12 · 2023: 11 · 2022: 20 · 2021: 18 · 2020: 10 · 2019: 2
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Development (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Institut Pasteur
- Centre National pour la Recherche Scientifique
- Ligue Nationale Contre le Cancer (PREAC2016.LCC)
- Association Française contre les Myopathies
- Laboratoire d'Excellence de Biologie pour la Psychiatrie (11-LABX-0035)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- BMP4, Smad signaling, dorsal interneurons, neural crest, roof plate, pluripotent stem cell-derived neurons, spinal cord development
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Humans, Interneurons, Neural Crest, Neurons, Organoids, Spine, Signal Transduction, Gene Expression Regulation, Developmental, Cell Lineage, Mice, Smad Proteins, Neural Tube, Bone Morphogenetic Protein 4, Induced Pluripotent Stem Cells
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