Sensory organs are essential for organisms to assess their environment. Our long- term goals are to understand the roles that non-neuronal glial-like cells play in the function and development of these organs, using the amphid sensory organ of the nematode C. elegans as a model. In multicellular animals, sensory structures are generally composed of both neurons and non-neuronal cells such as specialized glia. Loss of sensory structure function in humans due to disease, injury, or genetic defects has devastating effects not only on an individual's ability to interact with the environment, but also on physical and psychological well being. How sensory structures are assembled from neurons and glia during animal development is largely unknown. Furthermore, the roles played by non-neuronal cells in regulating the functions of sensory neurons are poorly understood. The amphid sensory organ of the nematode C. elegans is an excellent structure in which to study neuron-glia interactions during sensory organ development and function. The amphid is composed of 12 neurons, each with well-defined sensory roles, and two glial-like cells. Amphid architecture and molecular biology are remarkably similar to those of sensory organs in Drosophila and mammals. Furthermore, genetics and molecular biology are generally facile in C. elegans, allowing for discovery of conserved genes affecting amphid development and function. To understand the roles of glial cells in amphid sensory organ function we undertook a cell ablation approach in which one or both glial cells associated with the organ were removed at various times during the animals'life. Our results show that glia are absolutely essential for amphid sensory organ function. Specifically, we demonstrated that glia continuously regulate the shape of sensory endings of some neurons, but can also affect neuronal function without perturbing structure. Furthermore, these studies show that glia continuously produce (and secrete) proteins essential for sensory neurons to transduce environmental stimuli. From a microarray study, we identified 59 secreted/membrane proteins enriched in amphid glia. Here we propose to continue these studies by exploring two proteins in detail, FIG-1, and KCC-2. Both proteins are expressed specifically only in glia, and mutations in these proteins block sensory neuron function without any morphological alterations in either the neurons or the glia. We propose to: (1) Characterize the cell biology and function of FIG-1 to determine how it regulates neuronal activity. (2) Characterize the function of the KCl transporter KCC-2 in regulating neuronal activity. (3) Identify additional glial genes required for the function of C. elegans amphid sensory neurons. Together, these studies should provide important insight into how sensory neuron function is regulated by their associated non-neuronal glial cells.

Public Health Relevance

Sensory organs are important for interactions of humans with their environment, and defects in sensory organ function have debilitating effects on quality of life. Little is known about how non-neuronal cells of these organs promote organ function. Our studies will provide insight into sensory organ function, and delineate targets that might be used to develop treatments for persons with defects in sensory organ function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS064273-05
Application #
8299044
Study Section
Cellular and Molecular Biology of Glia Study Section (CMBG)
Program Officer
Gubitz, Amelie
Project Start
2008-09-30
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$360,150
Indirect Cost
$145,775
Name
Rockefeller University
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Rapti, Georgia; Li, Chang; Shan, Alan et al. (2017) Glia initiate brain assembly through noncanonical Chimaerin-Furin axon guidance in C. elegans. Nat Neurosci 20:1350-1360
Keil, Wolfgang; Kutscher, Lena M; Shaham, Shai et al. (2017) Long-Term High-Resolution Imaging of Developing C. elegans Larvae with Microfluidics. Dev Cell 40:202-214
Wang, Wendy; Perens, Elliot A; Oikonomou, Grigorios et al. (2017) IGDB-2, an Ig/FNIII protein, binds the ion channel LGC-34 and controls sensory compartment morphogenesis in C. elegans. Dev Biol 430:105-112
Singhal, Anupriya; Shaham, Shai (2017) Infrared laser-induced gene expression for tracking development and function of single C. elegans embryonic neurons. Nat Commun 8:14100
Singhvi, Aakanksha; Liu, Bingqian; Friedman, Christine J et al. (2016) A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape by Chloride Inhibition of an rGC. Cell 165:936-48
Wallace, Sean W; Singhvi, Aakanksha; Liang, Yupu et al. (2016) PROS-1/Prospero Is a Major Regulator of the Glia-Specific Secretome Controlling Sensory-Neuron Shape and Function in C. elegans. Cell Rep 15:550-562
Shaham, Shai (2015) Glial development and function in the nervous system of Caenorhabditis elegans. Cold Spring Harb Perspect Biol 7:a020578
Kelley, Melissa; Yochem, John; Krieg, Michael et al. (2015) FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis. Elife 4:
Kutscher, Lena M; Shaham, Shai (2014) Forward and reverse mutagenesis in C. elegans. WormBook :1-26
Pfaff, Samuel; Shaham, Shai (2013) Development of neurons and glia. Curr Opin Neurobiol 23:901-2

Showing the most recent 10 out of 26 publications