Biology Reference
In-Depth Information
maintenance of cellular motility, or for directed migration and target
finding. I will summarize here data from my laboratory that contributed to
an understanding of the molecular control of cell migration in the embryo.
Over the years, we analysed genes that control migration of two developing
cell types, neural crest cells and muscle progenitor cells. Both cell types are
released from epithelial structures, and in order to detach and become motile
they first undergo an epithelial-mesenchymal conversion. Mechanistically,
the release of the cells and their subsequent motility resembles the
process that is observed late during the progression of malignant
carcinomas. There, cells detach from the primary tumour by epithelial-
mesenchymal conversion and migrate in an uncontrolled manner to form
metastases at sites distant of the primary tumour. Because of the mechanistic
similarities, it is not so astonishing that genes implicated in tumour
progression play also important roles in cell migration events during
development. In particular, work from my laboratory demonstrated
that tyrosine kinase receptors implicated in tumorigenesis, like the c-ErbB
or c-Met tyrosine kinase receptors, turn out to control decisive steps in
migration of embryonic cells.
Migration of neural crest cells
Neural crest cells are released from the dorsal portion of the neural tube
during embryogenesis. The cells detach from the developing spinal cord and
hindbrain, and migrate in a stereotypical manner to various sites in the
embryo. Upon arrival at the targets, neural crest cells differentiate to form a
wide variety of different cell types: neurons and glia of the peripheral nervous
system, smooth muscle cells of the heart outflow tract, melanocytes, and also
cartilage and bone of the head (Le Douarin and Kalcheim, 1999). Upon
release from the neural tube, neural crest cells start to express a particular set
of genes, for instance ErbB3 or Sox10, which can be used to identify the cells
during migration.
ErbB receptors and their ligand, Nrg1
ErbB3 encodes a receptor of the type I family of tyrosine kinase receptors; the
prototype member of this family is ErbB1 also known as the EGF receptor.
ErbB receptors recognize specific ligands, which they bind with high a
nity.
Ligand binding leads to homo- or heterodimerization of ErbB receptors,
inducing their tyrosine kinase activity and the tyrosine phosphorylation of the
