During nervous system development, axons must grow and make proper connections with their targets within the body. In recent years, the discovery of numerous molecules that regulate this process has allowed us to make great strides in understanding how axons find their targets. Surprisingly, many of the molecules that guide axonal growth cones are conserved amongst extremely divergent organisms. For example, Netrin proteins regulate growth of axons toward the midline in a wide variety of organisms, from fruit flies to mice. To date, research has mainly concentrated on the similarities in axon guidance amongst organisms. Such discoveries, while fascinating, have failed to explain how different neural network patterns have arisen in divergent organisms. This investigation aims to examine the molecular mechanisms underlying the creation of novel axonal morphologies.
The specific aims of this investigation are: (1) to clone the netrin genes from Artemia franciscana and Parhyale hawaiensis, two crustaceans with extremely different axonal morphologies, (2) to analyze the expression patterns of these genes in relation to growing axons during Artemia and Parhyale development, and (3) to compare these expression patterns to those found in Drosophila melanogaster, a model organism in which the function of netrin genes is well documented. This work, particularly the analysis of Artemia, whose axons fail to grow toward the midline, will likely improve the basic understanding of how axonal guidance molecules can be used to create novel neural circuitry patterns. This could lead to a better understanding of how the complex neural circuitry patterns found in humans have arisen. Understanding the basic mechanisms that are used to create complex neural networks may someday enable us to recreate such complex networks in patients suffering from neural traumas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
3R15NS048904-01S1
Application #
7062992
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Riddle, Robert D
Project Start
2005-01-15
Project End
2007-06-30
Budget Start
2005-01-15
Budget End
2007-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$23,031
Indirect Cost
Name
Albion College
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
020884516
City
Albion
State
MI
Country
United States
Zip Code
49224
Clemons, Anthony; Haugen, Morgan; Le, Christy et al. (2011) siRNA-mediated gene targeting in Aedes aegypti embryos reveals that frazzled regulates vector mosquito CNS development. PLoS One 6:e16730
Clemons, Anthony; Mori, Akio; Haugen, Morgan et al. (2010) Culturing and egg collection of Aedes aegypti. Cold Spring Harb Protoc 2010:pdb.prot5507
Clemons, Anthony; Flannery, Ellen; Kast, Kristopher et al. (2010) Immunohistochemical analysis of protein expression during Aedes aegypti development. Cold Spring Harb Protoc 2010:pdb.prot5510
Clemons, Anthony; Haugen, Morgan; Flannery, Ellen et al. (2010) Fixation and preparation of developing tissues from Aedes aegypti. Cold Spring Harb Protoc 2010:pdb.prot5508
Haugen, Morgan; Tomchaney, Michael; Kast, Kristopher et al. (2010) Whole-mount in situ hybridization for analysis of gene expression during Aedes aegypti development. Cold Spring Harb Protoc 2010:pdb.prot5509
Clemons, Anthony; Haugen, Morgan; Flannery, Ellen et al. (2010) Aedes aegypti: an emerging model for vector mosquito development. Cold Spring Harb Protoc 2010:pdb.emo141
Duman-Scheel, M (2009) Netrin and DCC: axon guidance regulators at the intersection of nervous system development and cancer. Curr Drug Targets 10:602-10
Simanton, Wendy; Clark, Stephanie; Clemons, Anthony et al. (2009) Conservation of arthropod midline netrin accumulation revealed with a cross-reactive antibody provides evidence for midline cell homology. Evol Dev 11:260-8
Duman-Scheel, Molly; Clark, Stephanie M; Grunow, Eric T et al. (2007) Delayed onset of midline netrin expression in Artemia franciscana coincides with commissural axon growth and provides evidence for homology of midline cells in distantly related arthropods. Evol Dev 9:131-40