Michael Hortsch, Ph.D.Associate Professor of Cell and Developmental Biology | Phone: (734) 647-2720 Fax: (734) 763-1166 e-mail: hortsch@umich.edu |
Work in my laboratoryaddresses the role of neural cell adhesion molecules (CAMs) in the development,differentiation and functioning of nervous systems. The relative simplicityof its embryonic nervous system and its powerful genetics make the fruitflyDrosophila melanogaster an appealing organism for neurodevelopmental studies.Despite the huge evolutionary distance between insects and mammals themolecular and cellular analysis of their developing nervous systems hasprovided some astonishing parallels and similarities involving some highlyconserved gene families. One of the main interests of my lab is the furtherfunctional characterization of neural cell adhesion molecules, especiallyof L1 family members, which include Drosophila neuroglian, as well as L1-CAMs,CHL1s, Nr-CAMs, and neurofascins in vertebrate species. Research in my laboratory is mainlybased on a biochemical and immunological approach (such as the isolationof membrane proteins from embryonic extracts and the generation of mono-and polyclonal antibodies). It is complemented by molecular and classicalgenetic techniques (e.g. the use of PCR and yeast two-hybrid technologies,the generation of transgenic flies, and the characterization of mutationsin the Drosophila neuroglian and the human L1-CAM gene). Tissue culturecell transfection experiments combined with in vitro mutagenesis of clonedcDNAs are used for a more detailed structural and functional dissectionof these molecules. Of special interest is the role of CAMs as direct inducersof membrane cytoskeleton assembly which is a conserved feature which isshared by Drosophila neuroglian and human L1-CAM. We suspect that thisfunction may be important in the establishment of specialized neuronalcellular subdomains, such as axons, growth cones and dendrites. The identification and characterizationof CAMs and the characterization of their structural and functional propertieswill help us to understand how cell-cell interactions are involved in theformation of complex cellular systems such as the neuronal networks ofmetazoae. |   The protein domain structure characteristicfor members of the L1 family of neural cell adhesion molecules.See also the L1CAM Mutation Web Page. |
Phylogenetic tree of the L1 genefamily. Currently available L1 cDNA sequences were first alignedusing the multiple alignment option of the MacDNASIS® Pro 3.0 programpackage (Higgins-Sharp algorithm). The phylogenetic tree was constructedfrom these aligned sequences using the DNAMLK program from the PHYLIP programpackage [based on the maximum likelihood method described by Felsenstein(1981)].  Drosophila ankyrin is selectively recruitedto cell-cell contact sites in S2 cell aggregates expressing human L1-CAM.S2 cells expressing either human L1-CAM(Panel A) or the Drosophila neural CAM fasciclin I (Panel B) were allowedto aggregate and stained with a polyclonal rabbit anti-Drosophila ankyrinantibody, followed by a fluorescent secondary antibody. In contrast tosingle cells (arrowhead) or cell clusters expressing Drosophila fasciclinI, Drosophila ankyrin was recruited to cell contact sites in cell aggregatesexpressing human L1-CAM (arrow). Scale bar 10 micrometers. MDP-1 (Macrophage-Derived Proteoglycan-1)is a proteoglycan-type molecule which is produced by migratory embryonichemocytes and is detected in areas of basement membrane deposition in lateDrosophila embryos.MDP-1 immunostaining in a late embryonicstage 13 Drosophila embryo. These two composite photographs show the anterior(Panel A) and the posterior end (Panel B) of the same embryo facing thedorsal side. Arrowheads in panel A indicate MDP-1 staining around the brainlobes and in panel B the basement membrane lining of the hindgut. The arrowsin panel B point to the posterior spiracles which represent the terminalstructures of the larval tracheal tree. Scale bar 30 micrometers. The panel shows a sagittal view of thedeveloping nerve cord of a stage 13 Drosophila embryo.The anterior end of the embryo is tothe left. The arrows indicate the segmental pattern of the midline poresbetween the posterior commissure and the anterior commissure of the nextposterior segment. Arrowheads indicate an acellular, MDP-1-positive membranewhich surrounds the developing neuropile and is presumably identical withthe neural lamella.Representative Publications
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