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BMP4 patterns Smad activity and generates stereotyped cell fate organisation in spinal organoids
- Source :
- Development (Cambridge, England), Development (Cambridge, England), 2019, 146 (14), pp.dev175430. ⟨10.1242/dev.175430⟩, Development (Cambridge, England), Company of Biologists, 2019, 146 (14), pp.dev175430. ⟨10.1242/dev.175430⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- Bone Morphogenetic Proteins (BMP) 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 invivo, whether this is sufficient for pattern formation invitrois 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 cells 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 the study describes efficient methods to generate 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.
- Subjects :
- Organoid
MESH: Signal Transduction
[SDV]Life Sciences [q-bio]
MESH: Bone Morphogenetic Protein 4
MESH: Neurons
Smad Proteins
SMAD
Bone Morphogenetic Protein 4
MESH: Organoids
Pluripotent stem cells differentiation
Mice
0302 clinical medicine
MESH: Gene Expression Regulation, Developmental
MESH: Animals
Induced pluripotent stem cell
Cells, Cultured
Neurons
0303 health sciences
Neural crest
Gene Expression Regulation, Developmental
Cell Differentiation
Relay and associating spinal dorsal interneurons
MESH: Interneurons
Cell biology
[SDV] Life Sciences [q-bio]
Organoids
Patterning
medicine.anatomical_structure
Neural Crest
embryonic structures
MESH: Spine
Signal Transduction
MESH: Cells, Cultured
Self-organization
MESH: Cell Differentiation
Cell type
Neural Tube
animal structures
Induced Pluripotent Stem Cells
Cell fate determination
Biology
MESH: Induced Pluripotent Stem Cells
Bone morphogenetic protein
MESH: Neural Tube
03 medical and health sciences
Interneurons
Bone morphogenetic proteins
medicine
Animals
Humans
Cell Lineage
Molecular Biology
MESH: Mice
030304 developmental biology
MESH: Humans
Neural tube
MESH: Embryo, Mammalian
MESH: Smad Proteins
MESH: Cell Lineage
Embryo, Mammalian
MESH: Neural Crest
In vitro
Spine
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 09501991 and 14779129
- Database :
- OpenAIRE
- Journal :
- Development (Cambridge, England), Development (Cambridge, England), 2019, 146 (14), pp.dev175430. ⟨10.1242/dev.175430⟩, Development (Cambridge, England), Company of Biologists, 2019, 146 (14), pp.dev175430. ⟨10.1242/dev.175430⟩
- Accession number :
- edsair.doi.dedup.....d654fec2929ad62a0e5310f395ceca5e