The role of neurotrophins in development of neural-crest cells that become sensory ganglia

Abstract

A fundamental issue of neural-crest ontogeny is understanding how different types of cells are created at the right time and in the correct numbers. Sensory ganglia are among the many derivatives of the vertebrate neural crest. Their proper formation requires the regulation of several processes such as cell fate specification, proliferation, survival, and terminal differentiation. The timescale of the occurrence of processes involved in the regulation of cell number and identity, coincides with key morphogenetic events such as cell migration, homing and gangliogenesis. To gain insight into these processes, we characterized the cellular basis of metameric migration of neural-crest cells and of consequent ganglion organization, which are imposed by intrinsic differences within rostral and caudal sclerotomal compartments. We also established a transient requirement for neural tube-derived factors in regulating the proliferation, survival and differentiation of prospective DRG cells. Additionally, we showed that cooperation between the mesodermal cells and the neural tube is necessary for modulating cell number in the nascent ganglia. BDNF, NT-3 and basic FGF were found to mediate this environmental signalling. All the above factors display neurogenic activity for a subset of early-committed sensory neuron progenitors. This observation raises the possibility of an early redundancy in the response of individual neural-crest progenitors to distinct factors. This overlap in responsiveness progressively disappears upon the colonization of specific ganglionic sites and the subsequent establishment of selective innervation patterns by post-mitotic sensory neurons.