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MACKLIS LAB

Denis Jabaudon
Tina Lai

Arthur Czupryn

Liyun Li
Bartley Mitchell
Sanjay Magavi

Justine M. Nagurney

Kyle MacQuarrie
Alexander Eswar
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MGH-HMS Center for Nervous System Repair
Macklis Lab

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.

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