Cell adhesion is one of the most important properties controlling embryonic
development. Extremely precise cell-cell contacts are established according to the
nature of adhesion molecules that are expressed on the cell surface. The identification
of several families of adhesion molecules, well conserved throughout evolution,
has been the basis of a considerable amount of work over the past 20 years that
contributed to establish functions of cell adhesion in almost all organs. Nowadays,
cell adhesion molecules are not just considered as cellular glue but are thought to
play critical roles in cell signaling. Their ability to influence cell proliferation, migration,
or differentiation depends on both cell surface adhesion properties and activation
of intracellular pathways. The next challenge will be to understand how these
molecules interact with each other to ensure specific functions in the morphogenesis
of very sophisticated systems. Indeed, by exploring the cellular and molecular
mechanisms of nervous system development, the group of H. Fujisawa in Japan
identified in 1987 an adhesion molecule, neuropilin, highly expressed in the neuropile
of amphibian optic tectum. Ten years later, two groups discovered that neuropilin
is a receptor for guidance signals of the semaphorin family. Axon guidance is a
critical step during brain development and the mechanisms ensuring growth cone
navigation are beginning to be well understood. The semaphorins are bifunctional
signals defining permissive or inhibitory pathways sensed by the growth cone.
Moreover, a semaphorin can be repellent or attractive depending on the axonal populations.
The complexity of the signaling cascade triggered by the semaphorin is
further illustrated by the capacity of Sema3A to be repulsive for the axon and attractive
for the dendrites of cortical neurons. Hence, an appropriate response of the
growth cone requires the recruitment of a receptor complex enabling the integration
of this varying information. The analysis of the structure of neuropilin revealed a
very short intracellular domain lacking transduction capacities. Because of these
works, several groups started to analyze the possible interactions of neuropilin and
described various binding partners allowing semaphorin transduction. The current
view considers neuropilin as the heart of a receptor complex consisting of multiple
transmembrane molecules including tyrosine kinase receptors or other adhesion
molecules. In front of the growing implication of neuropilin during various physiologic
and pathophysiologic processes, we decided to edit this comprehensive book
designed to illustrate the diverse functions of this basic adhesion molecule. The first
part of the volume contains four Chapters presenting the discovery of neuropilin
and demonstrating its principal functions in the nervous, vascular and immune systems.
In the second part, four Chapters describe the molecular structure of neuropilin
and dissect the mechanisms ensuring receptor complex formation with various mol-
ecules such as the Plexins, the Vascular Endothelial Growth Factor Receptors or
other adhesion molecules such as L1. The last two Chapters focus on the pathophysiologic
implication of neuropilin especially for tumor progression and nervous
system lesions. More than an extensive description of a single molecule, this book
proposes a general model for the understanding of a multi-functional factor, a model
that may apply for a variety of signals. This volume illustrates how mechanisms are
conserved in the development of various biological systems, from the nervous system,
vascular system and immune system, how a single molecule is able to control
extremely precise cell behavior through specific interactions, and finally how dysfunction
of a particular signaling pathway may relate to disease. Understanding the
functions ensured by such specific molecular interactions will certainly have broad
implications for fundamental issues and clinical applications.
I would like to express my thanks to the authors who contributed in the production
of this book by providing excellent reviews enriched by multiple useful figures.
I would also like to thank R. Landes Bioscience and Kluwer Academic/Plenum
Publishers for publishing the book.