| Abstract |
In the developing nervous system neurons need to migrate often long distances to reach their final position and form the appropriate synaptic contacts. The migration of neurons takes place in two directions: radially and tangentially. In the region of the developing rhombencephalon many tangential migratory streams are observed. In this study we focused on two populations of neurons generated in the rhombic lip of rhombomeres 7 and 8 which migrate ventrally following two different migratory steams. The neurons of the caudal superficial migratory stream migrate just beneath the pial surface, cross the ventral midline and form the lateral reticular (LRN) and the external cuneate nucleus (ECN) at the contralateral side of their origin. The cells of the olivary stream migrate deep in the parenchyma and stop ipsilaterally against the floor plate to form the inferior olive nucleus (ION). First, in this study we use an in vitro assay for the culture of the region where these migrations take place and we analyze the morphology of the migrating cells of the superficial stream. We show evidence that these cells are preceded by long leading processes and during their migration they follow two different migratory patterns. At the beginning of their migration in the dorsal neural tube, they migrate in close apposition to each other and form distinct chains, whereas they disperse and follow Tuj-1 immunoreactive axons on reaching the ventral hindbrain. This suggests that, in the superficial stream, neuronal migration combines both homotypic and heterotypic mechanisms. We also show that the adhesion molecule TAG-1 is expressed by the migrating cells only during the period of migration. Blocking TAG-1 function results in alterations in the superficial migration, indicating that TAG-1 is involved in the superficial migration. Moreover, in TAG-1-deficient animals we observed fewer migrating cells at the superficial stream. Other members of the immunoglobulin superfamily and known ligands of TAG-1 are also expressed in the region of the migration but are not involved in the migration. These findings provide evidence that the TAG-1 protein is involved as a contact-dependent signal guiding not only axonal outgrowth but also cell migration probably via a homophilic type of interaction. The cells of the olivary migratory stream express the transcription factor Brn3.2 during their migration and after they settle to their final position. In this study,by using chick-quail chimeras, we provide evidence that not only the intrinsic fate of the migrating cells but also the environment of the migration is important for the formation of the appropriate nuclei. Moreover, we show that the floor plate exhibites a strong chemoattractive influence on both migratory streams that deviate from their normal path and follow the direction of ectopic floor plate fragments. In addition, the floor plate produces a short-range stop signal to the olivary cells which aggregate at both sides of this region. Ectopic sources of netrin can mimic the effect of the floor plate in the cell of the superficial migratory stream, which express the DCC netrin receptor during their migration. In contrast, the olivary cells express the DCC receptor when they are located near the rhombic lip and when they reach the midline, so ectopic netrin sources attract the olivary cells only when they are at the dorsal neural tube. In addition, we show evidence that the stop signal provided by the floor plate to the migrating olivary cells is probably the interaction between ephrin-B3, expressed by the floor plate, and EphA4, which is expressed by the migrating cells. In EphA4- deficient mice some cells of the inferior olive nucleus do not stopped before the floor plate and they are detected on the midline. In general, our findings provide evidence that both contact-dependent signals and chemoattractive cues influence the migration of the cells of the superficial migratory and olivary steams in the caudal medulla. Moreover, in this study we provide another example of common cues involved in both axonal guidance and cell migrations.
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Μελέτη των μηχανισμών μετανάστευσης κυττάρων στο προπαρεγκεφαλιδικό σύστημα
