We focus on the molecular and cellular signaling events that guide motor growth cones through a changing environment towards their synaptic partners (movie). In several genetic screens we have isolated a number of key genes essential for motor axon guidance. We have positionally cloned many of them to investigate their function at a cellular and molecular level. Through these studies we have defined several molecular pathway that produces transient and subtle changes in the extracellular matrix, thereby guiding growth cones. For example, one of these pathways produces a novel, receptor tyrosine kinase dependent signaling event that leads to the accumulation of chondroitin -sulfate proteoglycans exactly where growth cones make a characteristic turn. In the absence of this receptor tyrosine kinase signal, growth cones don’t make a turn and go astray.
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Jain, RA., Bell, H., Lim A., Chien, C.B. and Granato, M. 2014. Mirror movement-like defects in startle behavior of zebrafish DCC mutants are caused by abberant midline guidance of identified descending hindbrain neurons. J. Neuroscience (34), 2898-2909. pdf.
Sainath, R., Granato, M. 2013. Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish. PLoSONE.
Gordon, L.R., Gribble, K.D., Syrett, C. M. & Granato, M. 2012 . Initiation of synapse formation by Wnt-induced MuSK endocytosis. Development, 139, 1023-33.
Banerjee, S., Gordon, L., Donn, T.M., Berti, C., Moens, C.B., Burden, S.J. and Granato, M. 2011. A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration. Development, 138, 3287-96.
Jing, L, Lefebvre, J., Gordon, L. and Granato, M. 2009. Wnt signals organize synaptic prepattern and axon guidance through the unplugged/MuSk receptor. Neuron 61(5);721-33.
Lefebvre, J., Becaficco, S., Franzini-Armstrong, C. and Granato, M. 2007. Differential requirement for MuSK and Dystroglycan in generating patterns of neuromuscular innervation. PNAS,104(7):2483-8.
Palaisa, K. A. , Granato, M. 2007. Analysis of zebrafish sidetracked mutants reveals a novel role for plexin-A3 in intraspinal motor axon guidance. Development, 134(18), 3251-7.
Schneider, V. A. , Granato, M. 2006. The myotomal diwanka (lh3) glycosyltransferase and type VIII collagen are critical for motor growth cone migration. Neuron, 50, 1-13.