Eph-Ephrin Signaling and the Role of EFN-4 in Caenorhabditis Elegans Nervous Systems Development

<p>Eph receptor tyrosine kinases and their ephrin ligands are required for multiple aspects of nervous system development including axon outgrowth, synaptic plasticity, and the formation of topographic maps in the visual system. The <em>Caenorhabditis elegans </em>ephrin-A, <em>efn-4</em>, has a defined role in hypodermal patterning but its role in nervous system development is not well understood. We find that loss-of-function mutations in <em>efn-4</em> lead to suppression of axon branching in <em>C. elegans</em> model of X-linked Kallmann syndrome, a human genetic disorder that presents with loss of sense of smell and failure to undergo spontaneous puberty. In addition, <em>efn-4 </em>mutants have defects in AIY interneuron axon outgrowth. Tissue specific rescue experiments indicate that <em>efn-4</em> is required non-cell autonomously in the hypodermis to promote axon extension. Also, non-cell autonomous expression in the body wall muscle is sufficient to rescue anosmin-dependent axon branching, suggesting that primary axon outgrowth is genetically distinct from axon branching. Previous genetic and biochemical analyses failed to establish whether the canonical <em>C. elegans </em>Eph receptor, <em>vab-1</em>, functions as the <em>efn-4 </em>receptor during embryonic development. We show via biolayer interferometry that VAB-1 binds with high-affinity to EFN-4. Furthermore, EFN-4 binds with promiscuity to both the canoncial VAB-1 Eph receptor in <em>C. elegans </em>and additionally to at least one other binding partner the L1CAM (L1 Cell Adhesion Molecule) LAD-2. VAB-1 may have additional functional roles in guiding AIY primary neurite outgrowth to the central plexus. Our findings suggest EFN-4 is a key player in cell-to-cell communications that guide AIY neuronal projections.</p>

Name thesis:degree_name

Master of Science in Integrative Biology (MSIB)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2015

Author dc:creator

• Schwieterman, Alicia

Contributors dc:contributor

• Johnathan L. McMurry
• Susan M.E. Smith
• Scott J. Nowak

• Neurodevelopment
• Optical Biosensing
• Eph-ephrin Signaling
• Biology
• Integrative Biology

Repository record dc:identifier

https://digitalcommons.kennesaw.edu/integrbiol_etd/4

OAI identifier oai:identifier

oai:digitalcommons.kennesaw.edu:integrbiol_etd-1004