The strength of SMAD1/5 activity determines the mode of stem cell division in the developing spinal cord

The different modes of stem cell division are tightly regulated to balance growth and differentiation during organ development and homeostasis. However, the mechanisms controlling such events are not fully understood. We have developed markers that provide the single cell resolution necessary to ide...

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Bibliographic Details
Published in:The Journal of cell biology 2014-02, Vol.204 (4), p.591-605
Main Authors: Le Dréau, Gwenvael, Saade, Murielle, Gutiérrez-Vallejo, Irene, Martí, Elisa
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cell Cycle
Cell division
Cell Division - physiology
Cell Lineage
Cell Proliferation
Cellular biology
Chick Embryo - cytology
Chick Embryo - metabolism
Experiments
Flow Cytometry
Immunoenzyme Techniques
In Situ Hybridization
Neurons - cytology
Neurons - metabolism
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Smad1 Protein - genetics
Smad1 Protein - metabolism
Smad5 Protein - genetics
Smad5 Protein - metabolism
Spinal cord
Spinal Cord - cytology
Spinal Cord - metabolism
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
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Summary:The different modes of stem cell division are tightly regulated to balance growth and differentiation during organ development and homeostasis. However, the mechanisms controlling such events are not fully understood. We have developed markers that provide the single cell resolution necessary to identify the three modes of division occurring in a developing nervous system: self-expanding, self-renewing, and self-consuming. Characterizing these three modes of division during interneuron generation in the developing chick spinal cord, we demonstrated that they correlate to different levels of activity of the canonical bone morphogenetic protein effectors SMAD1/5. Functional in vivo experiments showed that the premature neuronal differentiation and changes in cell cycle parameters caused by SMAD1/5 inhibition were preceded by a reduction of self-expanding divisions in favor of self-consuming divisions. Conversely, SMAD1/5 gain of function promoted self-expanding divisions. Together, these results lead us to propose that the strength of SMAD1/5 activity dictates the mode of stem cell division during spinal interneuron generation.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201307031