Unraveling the differential dynamics of developmental fate in central and peripheral nervous systems.
Bone morphogenetic protein 2 (BMP2), differentially regulates the developmental lineage commitment of neural stem cells (NSC's) in central and peripheral nervous systems. However, the precise mechanism beneath such observations still remains illusive. To decipher the intricacies of this mechanism, we propose a generic mathematical model of BMP2 driven differentiation regulation of NSC's. The model efficiently captures the dynamics of the wild-type as well as various mutant and over-expression phenotypes for NSC's in central nervous system. Our model predicts that the differential developmental dynamics of the NSC's in peripheral nervous system can be reconciled by altering the relative positions of the two mutually interconnected bi-unstable switches inherently present in the steady state dynamics of the crucial developmental fate regulatory proteins as a function of BMP2 dose. This model thus provides a novel mechanistic insight and has the potential to deliver exciting therapeutic strategies for neuronal regeneration from NSC's of different origin.
Department of Chemistry, IIT Bombay, Powai, Mumbai - 400076, India.
Dola
D
Sengupta
Department of Chemistry, IIT Bombay, Powai, Mumbai - 400076, India.
Sandip
S
Kar
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002490:Central Nervous System / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008962:Models, Theoretical; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D017933:Peripheral Nervous System / Q000254:growth & development* / Q000378:metabolism
D055396:Bone Morphogenetic Protein 2