Expression of classical cadherins in the cerebellar anlage: Quantitative and functional aspects

During central nervous system (CNS) development, cell migration precedes and is key to the integration of diverse sets of cells. Mechanistically, CNS histogenesis is realized through a balanced interplay of cell-cell and cell-matrix adhesion molecules. Here, we summarize experiments that probe the developmental expression and potential significance of a set of cadherins, including M-, N- and R-cadherin, for patterning of the cerebellar cortex. We established a transgenic marker that allows cerebellar granule cells to be followed from the neuroblast stage to their final, postmitotic settlement. In conjunction with flow cytometry, this allowed us to derive a quantitative view of cadherin expression in differentiating granule cells and relate it to the expression of the same cadherins in cerebellar inhibitory interneuronal precursors. In vitro reaggregation analysis supports a role for cadherins in cell sorting and migration within the nascent cerebellar cortex that may be rationalized within the context of the differential adhesion hypothesis (Foty, R.A. and Steinberg, M.S., 2005. The differential adhesion hypothesis: a direct evaluation. Dev. Biol. 278, 255-263.).