Embryogenesis of the peripheral nervous system

Motor Within the ventral neural tube, populations of motor neuron progenitor cells are established by the interaction of a Sonic hedgehog signaling gradient with a series of transcription factors of the Gli, Pax, and Nkx groups. Cross-repressive interactions between pairs of transcription factors, such as Pax6/Nkx2.2 and Irx3/Olig2, refine the sites at which specific subpopulations of the motor neurons develop [38]. All progenitor motor neurons, visceral or somatic, form in the pMN region [32]. The visceral motor neurons that innervate the sympathetic ganglia settle in the intermediolateral columns of Terni. The somatic motor neurons that innervate the axial musculature settle in the medial and lateral subdivisions of the MMCs. All of the somatic motor neurons that innervate the limbs settle in the LMCs. The LIM code coordinates the following processes: (1) the settling position of the motor neurons within the medial and lateral subdivisions of the LMCs through cross-repressive interactions of Islet-1 and Lim1 proteins and (2) the selection of dorsal versus ventral trajectories for axon outgrowth through regulation of EphA4 receptors on the motor neurons and ephrin-A ligands in the mesenchymal cells of the limb [38]. The early-born neurons settle in the LMC_m and innervate ventrally derived limb muscles. The later-born neurons settle in the LMC _l and innervate dorsally derived limb muscles [38]. Specific combinations of ETS proteins and LIM proteins then specify those neurons that will form the motor pools of individual muscles. Sensory Populations of future neural crest cells arise at the neural plate border where there are high levels of both BMPs and Wnts (eg, Wnt6). They express specific transcription factors, such as FoxD3, and become neural crest. These then undergo epithelial- mesenchymal transition and migrate peripherally along defined routes. Neural crest cells that migrate ventrally are directed toward the anterior half of the sclerotome. Those that settle in relation to the anterior half of sclerotomes themselves form the sensory neurons of the dorsal root ganglia. Neural crest cells that migrate further ventrally establish the sympathetic chain ganglia, the neural clusters about the major branches of the aorta (eg, the celiac and superior mesenteric plexi), and the adrenal medulla. Neurons in the LMCs send out their axons through the ventral exit zone (ventral motor root). These questing axons navigate by means of a series of intermediate targets to reach the bases of the limbs. There, they pause in a waiting zone, "decide" their future courses, and selectively defasciculate or refasciculate to sort into fiber groups that will extend toward the appropriate targets within the limbs. The axons reach their specified targets, establish functional synapses with them, and overinnervate the target with redundant synapses. The target cells then refine their own synaptic connections by forcing the multiple different innervations to participate in a "use it or lose it," life-or-death competition for scarce neurotrophic factors that repress apoptosis. Only the most active synapses are able to take up sufficient neurotrophic factors to survive. The less functional synapses cannot repress apoptosis and die away. By these steps, the genetic programs within the fertilizing gametes use molecular biology to build a functional PNS.