Abstract
Author SummaryAs the vertebrate nervous system develops, neurons migrate from proliferation zones to their later place of function. Adhesion molecules have been implicated as key players in regulating cellular motility. In addition, the centrosome (the main microtubule organizing center of the cell) orients into the direction of neuronal migration. In this study we assign the trans-membrane adhesion molecule Cadherin-2 with an important function in the migration of granule neurons in the cerebellum, by interconnecting adhesion with directionality of migration. Time-lapse analysis in transparent zebrafish embryos revealed that Cadherin-2 enables granule neurons to form ‘chain’-like structures during migration. In addition, this adhesion molecule stabilized the position of the centrosome at the leading edge of the migrating neuron. In vivo tracing of a fluorescent Cadherin-2 reporter molecule showed that during individual migratory steps of a granule neuron, Cadherin-2 is shifted along the cell membrane in contact with chain-migrating neighboring neurons to the front compartment of migrating cells. Cadherin-2 is a crucial component of adherens junctions, which are connected via microtubules to the centrosome. We propose that the forward translocation of Cadherin-2-containing adherens junctions stabilizes the centrosome to the cell's front. Cadherin-2 thus transmits cell-cell contact modulation into directional migration of cerebellar granule neurons.
Highlights
The adhesion molecule family of classic cadherins is known to play important roles during many steps of central nervous system (CNS) development
Time-lapse analysis in transparent zebrafish embryos revealed that Cadherin-2 enables granule neurons to form ‘chain’-like structures during migration
Cadherin-2 is a crucial component of adherens junctions, which are connected via microtubules to the centrosome
Summary
The adhesion molecule family of classic cadherins is known to play important roles during many steps of central nervous system (CNS) development. Inactivation of Cadherin-2 in mice and zebrafish results in severe neural tube formation defects [6,7]. This lack of structural integrity makes it difficult to assess the specific functions of Cadherin-2 during later stages of brain differentiation. Conditional inactivation of Cadherin-2 in the CNS via application of function-interfering antibodies or dominant-negative variants have revealed crucial roles for this adhesion molecule in neural crest delamination [1,8]. Whereas classical studies have attributed Cadherin-2 function mostly to rigid cell-cell adhesion between stationary cells in mediating tissue integrity and segregation of different cell populations [10], the importance of Cadherin-2 in regulating cellular motility and in particular neuronal migration is emerging
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