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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


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.

Click 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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