Bradley
Molyneaux
Data from
our lab demonstrate that new neurons can be added to adult neocortical
circuitry from transplanted neural precursors or via manipulation
of endogenous precursors in situ. These data indicate that cellular
repair of damaged cortical and cortical output circuitry may be
possible, if we could understand the molecular controls over these
events. Given the heterogeneity of neuronal phenotypes in cortex,
and the complexity of their synaptic connections, attempts to
functionally repair neocortical circuitry will require detailed
understanding of signals that control differentiation, survival,
and connectivity of specific neuronal subtypes.
Paola Arlotta
and I have begun to address this issue by comparing gene expression
of three distinct kinds of purified cortical projection neurons
as they develop in vivo. In particular, we are interested in understanding
what are the genes that control both the initial specification
and further development of the clinically relevant class of corticospinal
motorneurons (CSMN). Using microarrays, we have identified genes
that distinguish CSMN from other related classes of cortical projection
neurons (e.g. callosal projection neurons and corticotectal projection
neurons). A subset of these largely uncharacterized genes, are
implicated in key developmental processes, from cell fate determination,
to axonal outgrowth, and cell and are all specifically expressed
in CSMN (positive markers) or excluded from CSMN (negative markers).
Most importantly some of these genes are functionally relevant
to the development of this specific neuronal subtype.