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Anjen Chenn, MD, PhDAssistant Professor
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To visit the Chenn Lab website click here.
Our major research interest is understanding the factors that control cell proliferation and differentiation in the developing mammalian central nervous system.
A fundamental question in developmental neurobiology is how an initially homogenous population of precursor cells expands and gives rise to the vast diversity of cells that comprise the mature brain. Understanding the control of cell division and the relationship between proliferation and differentiation has profound implications not only for developmental neuroscience, but also for disorders of the human nervous system. Problems in proliferation have been implicated in microcephaly (small brain), mental retardation, and schizophrenia, while misregulated proliferation can lead to cancer, cortical malformations, and epilepsy. Furthermore, an understanding of neuronal production from neural stem cells may offer potential therapy for neurodegenerative disease.
Asymmetric Divisions and Neuronal Production
Neurons in the mammalian central nervous system are generated from progenitor cells lining the lumen of the neural tube. Using time-lapse microscopy of dividing cells in slices of developing cerebral cortex, we have shown that cleavage orientation predicts the fates of daughter cells. Vertical cleavages produce behaviorally and morphologically identical daughters that resemble precursor cells; these symmetric divisions may serve to expand or maintain the progenitor pool. In contrast, horizontally dividing cells produce basal daughters that behave like young migratory neurons and apical daughters that remain within the proliferative zone. How the orientation of cell divisions is regulated during development remains unknown
Epithelial Organization and Cell Fate Determination
Although the mechanisms that regulate cell proliferation during neural development are poorly understood, studies in other tissues suggest that loss of normal cell polarity and tissue architecture play crucial regulatory roles in cell proliferation and cancer. Our most recent work suggests that beta catenin, an integral component of the adherens junction, can regulate cell cycle re-entry and differentiation in the developing mammalian brain. Transgenic mice expressing a truncated, stabilized form of beta catenin develop massively enlarged brains with increased cerebral cortical surface area and folds resembling sulci and gyri of higher mammals. Understanding the biology of epithelial organization can lend insight onto the regulation of proliferation during neural development and ultimately reveal mechanisms underlying developmental brain disorders and tumors in the central nervous system.
Windler-Hart SL, Chen KY and Chenn A. A cell behavior screen: identification, sorting, and enrichment of cells based on motility. BMC Cell Biology 2005, 6:14.
Stocker AM and Chenn A. Differential expression of alpha-E-catenin and alpha-N-catenin in the developing cerebral cortex. Brain Res. 2006 Feb 16;1073-1074:151-8. Epub 2006 Feb 2.
Woodhead, G., Mutch, C., Olson, E. C., and Chenn, A. Cell-Autonomous Beta-catenin Signaling Regulates Cortical Precursor Proliferation. J Neurosci. 2006 Nov 29;26(48):12620-30 (Featured as Paper of the Week in the Journal).
Noles, SR and Chenn, A. Cadherin inhibition of b-catenin signaling regulates the proliferation and differentiation of neural precursor cells. Molecular and Cellular Neuroscience 2007 Aug;35(4):549-58. Epub 2007 May 8.
Wrobel, CN, Swaminathan, S., Taketo, MM, and Chenn A. Persistent expression of stabilized b-catenin delays maturation of radial glial cells into intermediate progenitors. Developmental Biology, Sep 15;309(2):285-97. Epub 2007 Jul 24. PMCID: PMC2083700
Stocker, AM and Chenn A. Focal reduction of ÉøE-catenin causes premature differentiation and reduction of É¿-catenin signaling during cortical development. Developmental Biology, Apr 1, 2009; 328(1). Epub 2009 Jan 14. [cover illustration]. PMCID: PMC2674140 [Available on 2010/04/01]
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View Publications by Anjen Chenn listed in the National Library of Medicine (PubMed). |
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