|  Verne
S. Caviness, Jr., M.D., D.Phil.
Neuroscience Center at Massachusetts General
Hospital
Massachusetts General Hospital –
East
Building 149
13th Street
Charlestown, MA 02129
Telephone: 617-726-5621
E-mail: CAVINESS@HELIX.MGH.HARVARD.EDU
Biography
Dr. Caviness is the Joseph and Rose Kennedy
Professor of Child Neurology and Mental Retardation and Chief of Pediatric
Neurology. He received his undergraduate degree from Duke University,
D. Phil from the University of Oxford and M.D. from Harvard Medical
School. He joined the MGH in 1962 as a resident and became Professor
of Neurology in 1982.
Research Program
The general theme of current research projects in
the Caviness laboratory is examination of coordinate regulation of neocortical
neuronal laminar class specification and the process of progenitor cell
proliferation. The central hypothesis being pursued is that transcriptional
mechanisms regulatory to specification of neocortical neuronal laminar
class are coordinately regulated with mechanisms of cell output from
the progenitor cells and that p27Kip1 is a regulatory linkage in the
coordination. p27Kip1 is a cyclin dependent kinase inhibitor, which
operates during G1-phase of the cell cycle to induce cell cycle exit.
Prior work from this laboratory has led to the formulation
of a quantitative model of the proliferative process in mouse based
upon parameters of cell cycle kinetics and cell output. According to
this model the kinetic parameter TG1 (duration of the G1 phase of the
cycle) and the output parameter Q (the quiescent fraction, or the fraction
of postmitotic daughter cells that exits the cycle) are the only regulated
parameters in the neocortical neurogenetic sequence. Dr. Caviness’
group found that the transverse neurogenetic gradient of the pseudostratified
ventricular epithelium (PVE, the source of neocortical projection neurons)
corresponds closely to gradients of TG1 and Q, which are closely correlated
with each other in the PVE of normal mice. It was established by this
group that Q but not TG1 is increased by p27Kip1overexpression, using
a transgenic mouse model.
Moreover, this laboratory has shown preliminarily that
p27Kip1 overexpression advances the deep layer to superficial layer
class specification sequence, and that under these conditions the sequence
remains correlated with Q but not with TG1. It was found further that
a substantial number of signal transduction and cell cycle related transcripts
were also expressed according to gradients that correlate with the gradients
of TG1 and Q in the normal PVE.
Current work from this laboratory focuses on three specific
areas:
1. Neocortical neuron laminar class specification and production profiles
correlate with the proliferative output parameter Q and not with the
kinetic parameter TG1.
2. Region-specific coordination of laminar class specification and production
profiles, TG1 and Q by the transcription factor Emx2 by upregulation
of p27Kip1 expression.
3. Coordinate regulation of Q and expression patterns of a restricted
but large set of transcripts.
Publications
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here to access a full PubMed search on Dr. Caviness
- Goto T, Takahashi T, Miyama S, Nowakowski RS, Bhide PG, Caviness
VS. (2002) Developmental regulation of the effects of fibroblast
growth factor-2 and 1-octanol on neuronogenesis: implications for
a hypothesis relating to mitogen-antimitogen opposition. J Neurosci
Res 69:714-722.
- Takahashi T, Caviness VS, Bhide PG (2002) Analysis of cell generation
in the telencephalic neuroepithelium. Methods Mol Biol 198:101-113
Caviness VS, Goto T, Tarui T, Takahashi T, Bhide
PG, Nowakowski RS (2003) Cell output, cell cycle duration and neuronal
specification: a model of integrated mechanisms of the neocortical
proliferative process. Cereb Cortex 13:592-598.
- Mitsuhashi T, Aoki Y, Eksioglu YZ, Takahashi T, Bhide PG, Reeves
SA, Caviness VS. (2001) Overexpression of p27Kip1
lengthens the G1 phase in a mouse model that targets inducible gene
expression to central nervous system progenitor cells. Proc Natl Acad
Sci U S A 98:6435-6440
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