Department of Zoology

 

Developmental Biology

Matthias Landgraf

University Lecturer

Email: ml10006@cam.ac.uk

Tel.: +44 (0)1223 336635

Our goal is to understand the mechanisms that underlie the development of neural circuits and the emergence of coordinated function. We use the embryonic nervous system of Drosophila as a model, which has been extremely influential for our understanding of mechanisms of neurogenesis and axon guidance. We focus on the development of the motor network that generates the simple crawling movements of the Drosophila larva.

Mechanisms underlying the development of neuronal lineages

Neural progenitor cells are the fundamental developmental modules of nervous systems. However, the diversity that is actually generated within progenitor cell lineages and the underlying developmental mechanisms and organisational principles remain to be established. The most crucial cellular characteristics of neuronal differentiation are projection patterns and the transmitters released. We are exploring the patterns and underlying mechanisms with which projection and transmitter phenotypes are specified as neuronal lineages develop.

Organised growth of axons and dendrites

We study the mechanisms that regulate the growth, branching and targeting of postsynaptic dendritic arbors. We have shown that the terminal phases of growth in both axons and dendrites depend on the responses of individual neurons to positioning cues in the mediolateral and dorsoventral axes of the developing nervous system. We have identified these cues and shown that axons and dendrites respond to them by growing to specific locations within the network in an autonomous, target independent fashion. The implication of these findings is that the terminals of connecting pre- and postsynaptic partners are delivered autonomously to common localised volumes of the neuropile within which connections will subsequently form.

Homeostatic control of connectivity

We have made an experimental analysis of the factors that govern the formation of these connections. As expected we find that contact with putative presynaptic partners is a significant factor in determining patterns of postsynaptic growth and branching. In normal development the growth of dendrites slows as activity in the network is first observed. Similarly, genetic manipulations that increase the number of presynaptic contacts reduces arbor size. Conversely, dendritic growth is enhanced when synaptic activity is blocked or neurotransmitter is absent. Thus we detect, at a cellular level, a homeostatic mechanism that regulates the interaction between pre- and postsynaptic partners as synaptic signalling between them begins.

Funding
Our research is supported by a variety of funding agencies, including The Royal Society, The Wellcome Trust, The Gates Cambridge Trust, The Katsia Foundation, Fondation Fyssen, and a Henslow Research Fellowship.

Selected publications

  • Nicolaï, L.J., Ramaekers, A., Raemaekers, T., Drozdzecki, A., Mauss, A.S., Yan, J., Landgraf, M., Annaert, W., Hassan, B.A., 2010. Genetically encoded dendritic marker sheds light on neuronal connectivity in Drosophila. Proc Natl Acad Sci USA 107, 20553-20558.
  • Mauss, A., Tripodi, M., Evers, J.F. and Landgraf, M. (2009).  Midline signalling systems direct the formation of a neural map by dendritic targeting in the Drosophila motor system. PLoS Biol 7, e1000200.
  • Tripodi, M., Evers, J.F., Mauss, A., Bate, M. and Landgraf, M. (2008).  Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input. PLoS Biol 10, E260.
  • Diegelmann, S., Bate, M. and Landgraf, M. (2008).  Gateway cloning vectors for the LexA-based binary expression system in Drosophila. Fly 2, 236-239.
  • Ou, Y., Chwalla, B., Landgraf, M. and van Meyel, D.J. (2008) [joint senior authors].  Identification of genes influencing dendrite morphogenesis in developing peripheral sensory and central motor neurons.  Neural Development 3, 16.
  • Roy, B., Singh, A.P., Shetty, C., Chaudhary, V., North, A., Landgraf, M., Vijayraghavan, K., Rodrigues, V.  (2007).  Metamorphosis of an identified serotonergic neuron in the Drosophila olfactory system. Neural Development 2, 20.
  • Landgraf, M. and Thor, S. (2006a). Development and structure of motoneurons. In: The Fly Neuromuscular Junction: Structure and Function,  (ed. V. Budnik and C. Ruiz-Canada), San Diego, Elsevier Academic Press, International Review of Neurobiology 75: 33-53.
  • Landgraf, M. and Thor, S. (2006b). Development of motoneurons: specification and dendritic morphology. In: Drosophila as a model for understanding development and function of the Central Nervous System,  (ed. R. A. Baines and M. Landgraf), Seminars in Cell and Developmental Biology 17:3-11.
  • Landgraf, M. and Evers, J.F. (2005). Control of dendritic diversity. Curr Opin Cell Biol 17:690-696.
  • Landgraf, M., Jeffrey, V , Fujioka, M., Jaynes, J.B. and Bate, M. (2003) Embryonic Origins of a Motor System: Motor Dendrites Form a Myotopic Map in Drosophila. PLoS  Biol 1, E41.
  • Zlatic, M., Landgraf, M. and Bate, M. (2003) Genetic specification of axonal arbors: atonal regulates robo3 to position terminal branches in the Drosophila nervous system. Neuron. 37:41-51.
  • Landgraf, M., Sanchez-Soriano, N., Technau, G.M., Urban, J. and Prokop, A. (2003) Charting the Drosophila neuropile: a strategy for the standardised characterisation of genetically amenable neurites. Dev Biol. 260:207-25.:133-141
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