title: Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance.
abstract: The extension of long slender axons is a key process of neuronal circuit formation, both during brain development and regeneration. For this, growth cones at the tips of axons are guided towards their correct target cells by signals. Growth cone behaviour downstream of these signals is implemented by their actin and microtubule cytoskeleton. In the first part of this Commentary, we discuss the fundamental roles of the cytoskeleton during axon growth. We present the various classes of actin- and microtubule-binding proteins that regulate the cytoskeleton, and highlight the important gaps in our understanding of how these proteins functionally integrate into the complex machinery that implements growth cone behaviour. Deciphering such machinery requires multidisciplinary approaches, including genetics and the use of simple model organisms. In the second part of this Commentary, we discuss how the application of combinatorial genetics in the versatile genetic model organism Drosophila melanogaster has started to contribute to the understanding of actin and microtubule regulation during axon growth. Using the example of dystonin-linked neuron degeneration, we explain how knowledge acquired by studying axonal growth in flies can also deliver new understanding in other aspects of neuron biology, such as axon maintenance in higher animals and humans.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK. Andreas.Prokop@manchester.ac.uk
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokop
authors.forename: Robin
authors.initials: R
authors.lastname: Beaven
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.forename: Natalia
authors.initials: N
authors.lastname: Sánchez-Soriano
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins
keywords: Actin; Axon; Brain disorders; Cytoskeleton; Drosophila; Growth cone; Microtubule