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Work in my laboratory addresses the role of neural
cell adhesion molecules (CAMs) in the development, differentiation
and functioning of the nervous system. The relative simplicity of
its embryonic nervous system and its powerful genetics make the
fruit fly Drosophila melanogaster an appealing organism for neurodevelopmental
studies. Despite the huge evolutionary distance between insects
and mammals the molecular and cellular analysis of their developing
nervous systems has provided some astonishing parallels and similarities
involving some highly conserved gene families. One of the main interests
of my lab is the further functional characterization of neural CAMs
belonging to the L1 family, which includes Drosophila neuroglian,
as well as L1-CAMs, Nr-CAMs, and Neurofascins in vertebrate species.
L1-type CAMs directly interact with multiple other cellular proteins
and are potent inducers of signaling processes, which result in
neurite outgrowth and axonal pathfinding. We are currently in the
process of unraveling the complex functional features of L1-type
CAMs and trying to understand why mutations in the human L1-CAM
gene result in mental retardation and other neurological phenotypes.
Our research is mainly based on a biochemical and immunological
approaches (such as the isolation of membrane proteins from embryonic
extracts and the generation of mono- and polyclonal antibodies).
These are complemented by molecular and classical genetic techniques
(e.g. the use of PCR and yeast two-hybrid technologies, the generation
of transgenic flies, and the characterization of mutations in the
Drosophila neuroglian and the human L1-CAM gene). Tissue culture
cell transfection experiments combined with in vitro mutagenesis
of cloned cDNAs are used for a more detailed structural and functional
dissection of these molecules.
The identification and characterization of CAMs and the characterization
of their structural and functional properties will help us to understand
how cell-cell interactions are involved in the formation of complex
cellular systems such as the neuronal networks of metazoae.
:
- Godenschwege, L.V. Kristiansen, S.B. Uthaman, X. Shan-Crofts, P. Carruccio, M. Hortsch, R.K. Murphey. 2006 A Conserved Role for Drosophila Neuroglian and human L1-CAM in Central Synapse Formation. Current Biology 16: 12-23.
- L.V. Kristiansen, E. Velasquez, S. Romani, S. Baars, V. Berezin, E. Bock, M. Hortsch, and L. Garcia-Alonso. 2005. Genetic Analysis of an Overlapping Functional Requirement for L1- and NCAM-type Proteins During Sensory Axon Guidance in Drosophila. Mol. Cell. Neurosci. 28: 141-52 (featured on the cover of the journal)
- C. Faivre-Sarrailh, S. Banerjee, J. Li, M. Hortsch, M. Laval, and M.A. Bhat. 2004. Drosophila contactin, a homolog of vertebrate contactin, is required for septate junction organization and paracellular barrier function. Development 131: 4931-42.
- Wei, M. Hortsch, and S. Good. 2004. Neuroglian Stabilizes Epithelial Structure during Drosophila Oogenesis. Dev. Dynamics 230: 800-8. (featured on the cover of the journal)
- R. Islam, L.V. Kristiansen, S. Romani, L. Garcia-Alonso, and M. Hortsch. 2004. Activation of EGF Receptor Kinase by L1-mediated Cell Adhesion. Mol. Biol. Cell 15: 2003-12.
- Islam, R., S.-Y. Wei, W.-H. Chiu, M. Hortsch, and J.-C. Hsu.
2003. Neuroglian activates Echinoid to antagonize the Drosophila
EGF receptor signaling pathway. Development. 130:2051-9.
- Hortsch, M., K.L. Paisley, M.Z. Tian, M. Qian, M. Bouley, and
R. Chandler. 2002. The axonal localization of large Drosophila
ankyrin2 protein isoforms is essential for neuronal functionality.
Mol. Cell. Neurosci. 20:43-55. (featured on the cover of the journal)
- Hortsch, M. 2000. Structural and functional evolution of the
L1-family: Are four adhesion molecules better than one? Mol.
Cell. Neurosci. 15:1-10.
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