Paola
Arlotta
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.
Brad Molyneaux
(an MD-Ph.D student in the lab) 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.