Marta Paterlini

Marta Paterlini
Department of Cell and Molecular Biology (CMB)
This e-mail address is being protected from spambots. You need JavaScript enabled to view it

 

Phylogenetic fate mapping in the human brain

The hippocampus is critical for learning and memory and heavily affected in psychiatric and neurodegenerative diseases. The presence of stem cells in this structure has led to an increased interest in the phenomenon of adult neurogenesis and its role in hippocampal functioning. Although causal relationships have not been established, many factors known to impact neurogenesis in the hippocampus are implicated in the pathogenesis of depression and neurological diseases. Also, adult neurogenesis has been proposed to reflect a "neurogenic reserve" that may determine vulnerability to hippocampal dysfunction and neurodegeneration.

Our lab meets the challenge to elucidate these processes in the normal and pathological brain. Indeed, despite the knowledge of the occurrence of neurogenesis in the region of the dentate gyrus of the hippocampus in humans, nothing is known really about its origin and function. In fact, despite many studies on adult neurogenesis in the dentate gyrus in animals, the same type of analysis in humans has been difficult. We would like to tackle form a completely new prospective, defining a single cell phylogenetic fate mapping.

Progress has been made in the generation of a retrospective fate map at the single cell level in higher organisms such as mouse and human. It is known that new mutations arise in the genome of somatic cells with almost every cell division and this could be exploited to define their inheritance pattern, which will reflect their hierarchical relationship. Using phylogenetic analysis, analogous to that used to extrapolate evolutionary relationship between species, the hierarchy between cells in a tissue can be determined.

We aim to apply these innovative methods to retrospectly map cell fate within the adult mammalian brain. To start with, single cell fate mapping analysis will provide in situ data on the extent and pattern of adult neurogenesis in the dentate gyrus.

5 Selected publications:

W.S. Lai, B. Xu, K.G.C. Westphal , M. Paterlini, B. Olivier, P. Pavlidis, M. Karayiorgou and J.A. Gogos Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning. PNAS (2006) 103(45): 16906-11 M.

Paterlini, S.S. Zakharenko, W.S. Lai, J. Mukai, K.G.C. Westphal, B. Olivier, D. Sulzer, Siegelbaum, M. Karayiorgou & J.A. Gogos Transcriptional and behavioral interaction between 22q11.2 genes modulates schizophrenia-related phenotypes. Nature Neuroscience. (2005) 8(11): 1586-1594

M. I. Aller, A. Jones, D. Merlo, M. Paterlini, A.H. Meyer, U. Amtmann, S. Brickley, H.E. Jolin, A.N.J. McKenzie, H. Monyer, M. Farrant, W. Wisden Cerebellar granule cell Cre recombinase expression. Genesis. (2003) 36(2): 97-103

M. Paterlini, V. Revilla, A.L. Grant and W. Wisden Expression of the neuronal calcium sensor protein family in the rat brain. Neuroscience. (2000) 99(2): 205-16

M. Paterlini, A. Valerio, F. Baruzzi, M. Memo and P.F. Spano Opposing regulation of tau protein levels by ionotropic and metabotropic glutamate receptors in human NT2 neurons. Neuroscience Letters (1998) 243: 77-80