The role of neurotrophins during early development.

The effects of neurotrophins during the middle and late stages of development are well known. It was previously thought that neurotrophins had no role during early development, but this is not the case and is the subject of this review article. The earliest neurotrophin receptor expressed is that for neurotrophin-3 (NT-3). TrkC is detected in the neural plate and is present in the neural tube. Initially, the distribution of TrkC is homogenous, but it becomes localized to specific regions of the neural tube as the neural tube differentiates. The receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), TrkB, is detected somewhat later than TrkC in the neural tube where it is also differentially localized. In contrast, the NGF receptor, TrkA, was not detected during early development. Both NT-3 and BDNF have been shown to have effects in vitro during early development. NT-3 caused an increase in neurite outgrowth and apoptosis in neural plate explants, and promoted differentiation of progenitors into motoneurons. BDNF increased the number of motoneurons in neural tube explants. These data suggest that NT-3 and BDNF may play a role during early development in vivo.