Many neurons receive information through elaborate dendritic arbors. The formation of dendritic arbors is under genetic control and the form of dendritic arbors correlates with function. Importantly, some forms of mental retardation have been linked to defects in dendrite development. Work in both Drosophila and vertebrates has shown that dendrite arborization is under control of dedicated transcriptional networks, the extracellular matrix and genes involved in the regulation of Golgi dynamics. The PVD sensory neurons in C. elegans were recently established as a powerful genetic system to study dendrite branching during development. In an unbiased forward genetic screen we have identified a novel, previously unstudied gene that is conserved from worms to mammals and acts in the tissues surrounding the dendrites. In this application we are using an approach that integrates both C. elegans genetics and biochemical experiments to explore for the first time the function of this gene in dendrite development. Specifically, we will determine whether the function of this gene is also required for development of other branched and unbranched neurites in C. elegans. Additionally, we will identify the vertebrate homologs of this gene. In a second series of experiments, we will determine the genetic and biochemical relationship between the newly identified gene and a transmembrane receptor that we have identified as a putative receptor that acts in neurons. Understanding such fundamental processes as dendrite development is a prerequisite for the eventual development of therapeutic and diagnostic approaches for conditions in which dendrites develop incorrectly.

Public Health Relevance

Nerve cells receive their input by way of elaborately branched structures termed dendrites which are defective in numerous pathological conditions such as certain forms of mental retardation. The genetic cause for these defects is often poorly understood, yet a thorough understanding of the genetic basis is the prerequisite for any eventual therapeutic intervention. Here we propose to investigate the function of a novel, previously unstudied gene that is required for dendritic arbor formation using a combination of C. elegans genetics and biochemical approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS081505-01A1
Application #
8583828
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Mamounas, Laura
Project Start
2013-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$208,750
Indirect Cost
$83,750
Name
Albert Einstein College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Salzberg, Yehuda; Ramirez-Suarez, Nelson J; B├╝low, Hannes E (2014) The proprotein convertase KPC-1/furin controls branching and self-avoidance of sensory dendrites in Caenorhabditis elegans. PLoS Genet 10:e1004657
Levi-Ferber, Mor; Salzberg, Yehuda; Safra, Modi et al. (2014) It's all in your mind: determining germ cell fate by neuronal IRE-1 in C. elegans. PLoS Genet 10:e1004747
Salzberg, Yehuda; Diaz-Balzac, Carlos A; Ramirez-Suarez, Nelson J et al. (2013) Skin-derived cues control arborization of sensory dendrites in Caenorhabditis elegans. Cell 155:308-20