Development of the mesencephalic nucleus of the trigeminal nerve in chick embryos: target innervation, neurotrophin receptors, and cell death.

The goal of this study was to determine whether processes of neurons in the mesencephalic nucleus of the trigeminal nerve (Mes V) of chick embryos arrive in their peripheral target prior to the period of developmental cell death, and to determine whether neurons with early target contact survive to a greater extent than neurons with processes that reach their peripheral target later. The arrival of Mes V nerve fibers in the masticatory muscles was determined by injecting the fluorescent tracer DiI, and the position of labeled and unlabeled neurons was mapped in subdivisions of the Mes V nucleus. Developmental changes in the numerical configuration of Mes V subdivisions were studied in DiI-labeled as well as Nissl-stained material. The expression of low-affinity (p75) neurotrophin receptors was investigated throughout development of the Mes V nucleus with in situ hybridization to assess whether and how levels of expression of this trophic receptor may relate to target innervation and cell death. The extent of cell death was evaluated by counting pyknotic nuclei. Processes of Mes V neurons invade their peripheral target between 5 and 7 days of incubation (E5-7). At E7-12, between 800 and 1,400 labeled Mes V neurons were distributed throughout the two main subdivisions of the Mes V nucleus, the tectal commissure and the optic tectum. Only few Mes V neurons were labeled in the posterior commissure or outside the brain. Cell counts in Nissl-stained material from E7-13 revealed that the numbers of Mes V neurons in the optic tectum decreased to about 40-60%, and in the tectal commissure to 20-25%, whereas Mes V neurons in the posterior commissure disappeared almost entirely. Few Mes V neurons remained in the leptomeninges at E8-10, but a considerable number was found outside the midbrain at E11, indicating ongoing migration of some Mes V neurons. Neurotrophin receptors were differentially expressed in the Mes V nucleus: Before and after the period of cell death, 90-100% of Mes V neurons expressed neurotrophin receptors, whereas during, and immediately preceding the period of developmental cell death (E9-E13), merely 70% of Mes V neurons expressed this receptor. These findings are consistent with the hypothesis that early target contact may provide an advantage for the survival of Mes V neurons and that competition for trophic factors may occur in the peripheral target of this nucleus prior to the period of cell death.