title: The strength of SMAD1/5 activity determines the mode of stem cell division in the developing spinal cord.
abstract: 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.
authors: Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Parc Científic de Barcelona, Barcelona 08028, Spain.
authors: Gwenvael
authors: G
authors: Le Dréau
authors: Murielle
authors: M
authors: Saade
authors: Irene
authors: I
authors: Gutiérrez-Vallejo
authors: Elisa
authors: E
authors: Martí
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology*; D019070:Cell Lineage; D049109:Cell Proliferation; D002642:Chick Embryo / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism*; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051898:Smad1 Protein; D051902:Smad5 Protein