Disorders of motility are among the most common and debilitating
neurological ailments. In most cases, treatment of these conditions is at best
palliative. This is mainly due to the apparent inability of central neurons to
regenerate after a given noxious event. In the past, embryos have proven to be
valuable objects to study the mechanisms of growth and death in nerve cells
since both are physiological events in the developing nervous system. The
discovery and study of an ever-growing list of molecules that are involved in
these events has significantly furthered our understanding of the conditions
that have to be met for individual nerve cell populations to develop into
functional structures. It also has the potential to contribute significantly to the
establishment of more targeted and efficient therapeutic strategies.
Here, the effects of macrophage-stimulating protein (MSP) and 7-
synuclein on two systems in the developing brainstem involved in controlling
movement have been studied: a) the cranial motoneurons and b) the
dopaminergic neurons of the substantia nigra and the ventral tegmental area.
MSP exerts a variety of biological actions on many cell types, but has no
known functions in the brain. To investigate whether MSP is also capable of
acting as a neurotrophic factor, hypoglossal motoneurons were purified from
the embryonic chicken hindbrain because these neurons are known to express
the MSP receptor tyrosine kinase RON. The study shows that MSP promotes
the in vitro survival of these neurons during the period of naturally occurring
neuronal cell death and enhances the growth of neurites from these neurons.
Furthermore, MSP mRNA was detected in the developing tongue which is the
target tissue for hypoglossal neurons. These studies demonstrate that MSP is a
neurotrophic factor for a distinct population of developing motoneurons.
γ-synuclein is a recently discovered member of the synuclein family.
Another member of this family, a-synuclein has been implicated in the
pathogenesis of Parkinson's disease. However, little is known about the
function of γ-synuclein and it has not yet been directly implicated in the
genesis of neurodegenerative conditions. Here, brainstems of transgenic mice
lacking γ-synuclein have been analysed by means of immunohistochemical
and histological techniques. The data obtained shows that γ-synuclein is
expressed in the murine substantia nigra and in most cranial motor nuclei and
that the localization of the protein undergoes a shift during development from
a cytosomal to an axonal and synaptic localization. Mice lacking γ-synuclein
have a deficit of neurons in these structures. In the context of recent studies
which have revealed in vivo and in vitro interactions between the synucleins,
this data suggests that a fine balance between α- and γ-synuclein seems
critical to prevent the demise of certain neurons during the period of naturally
occurring neuronal cell death. It also indicates that γ-synuclein may play a
role in the pathogenesis of Parkinson's disease