Borodinsky LN , Belgacem YH , Swapna I , Visina O , Balashova OA , Sequerra EB , Tu MK , Levin JB , Spencer KA , Castro PA , Hamilton AM , Shim S .

R01 NS073055 NINDS NIH HHS , R01NS073055 NINDS NIH HHS

             axon guidance
             neurogenesis
             synapse maturation

Figure 1. Interplay between Ca2+ spike activity and morphogenetic proteins in the developing spinal cord. (A) BMP signaling recruits p38 MAPK that phosphorylates and inhibits Nav1.6, thus decreasing Ca2+ spikes in embryonic spinal neurons. Low levels of Ca2+ spike activity are necessary for the specification of dorsal commissural spinal neurons through a Smad1/5/8‐dependent mechanism. Based on the study by Swapna and Borodinsky (2012). (B) Shh activates Smo, which recruits PLC leading to IP3 transients that correlate with TRPC1 and Cav‐mediated Ca2+ spikes that regulate neurotransmitter specification in developing spinal neurons. Based on the study by Belgacem and Borodinsky (2011). (C) The opposing dorsoventral gradients of BMP and Shh generate a gradient of Ca2+ spike activity that is important for spinal neuron differentiation. Ptc: Patched1; Smo: Smoothened; PLC: phospholipase C.

Figure 2. Integration of diverse developmental cues by second messenger signaling. Morphogenetic proteins, neural activity and environmental factors all converge in characteristic second messenger dynamics that vary from global to localized as neural cells differentiate and mature. The kinetics of second messenger signaling are developmentally regulated due to temporal changes in developmental cues and in expression and activation profiles of ion channels and signaling molecules.

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