The aim of this study was to describe and analyze the regulation and spatio-temporal
dynamics of melanocyte migration in vitro and its coupling to cell
division and interaction with the matrix. The melanocyte lineage is particularly
interesting because it is involved in both embryonic development and
oncogenesis/metastasis (melanoma). Biological experiments were performed on two melanocyte
cell lines established from wild-type and β-catenin-transgenic mice
(bcat*). The multi-functional β-catenin molecule is known to be able to
regulate the transcription of various genes involved in cell proliferation and migration,
particularly in the melanocyte lineage. We also investigated fibronectin, an
extra-cellular matrix protein that binds integrins, thereby providing adhesion points for
cells and encouraging migration. As the migration of individual cells were followed,
automated methods were required for processing the large amount of data generated by the
time-lapse video-microscopy. A model-based approach for automated cell tracking was
evaluated on a sample by comparison with manual tracking. This method was found reliable
in studying overall cell behaviour. Its application to all the observed sequences provided
insight into the factors affecting melanocyte migration in vitro:
melanocytes of mutated form of β-catenin showed higher division rates and
no contact inhibition of growth was induced by the resulting increase in cell density.
However, cell density limited the amplitude of cell displacements, although their motility
was less affected. The high fibronectin concentration bound to substratum promoted cell
migration and motility, the effect being more intense for wild-type cells than for cells
with β-catenin over-expression. During the division process, cell
migration speed increased rapidly then decreased slowly. Analyses of such data is expected
to lead both to biological answers and to a framework for a better modeling processes in
the future.