Figure 9.

Model for how Merkel cell-derived BDNF specifies SAI neuron molecular and electrophysiological phenotypes. In wild-type mice (left side), BDNF released from embryonic Merkel cells binds TrkB expressed on SAI neuron peripheral terminals, initiating signaling cascades that induce expression of the transcription factors Egr1, Fos, Nr4a1, Tbx3, Cux2, MafA, and Sall1. Fos maintains TrkC expression (Hughes and Dragunow, 1995), Egr1 initiates and MafA maintains Ret expression (Andrew et al., 2002; Bourane et al., 2009), and transcription factors like Cux2 coordinate ion channel expression (Bachy et al., 2011), all of which contribute to SAI neuron excitability and mature electrophysiological properties. In contrast, BDNF deletion during the embryonic period (right side) prevents the activation of these signaling cascades, which in turn leads to failed expression of TrkC and Ret along with misexpression of ion channels.