Morphogenesis of Dendrites That Form Specialized Contacts With Glia
Cebul, Elizabeth Rose Lamkin
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CitationCebul, Elizabeth Rose Lamkin. 2020. Morphogenesis of Dendrites That Form Specialized Contacts With Glia. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractCells assemble into tissues by forming precise contacts with specific neighbors. Nowhere are cell junctions more fascinating than in the nervous system, where cells develop intricate morphologies in order to build connections required for neural function. While neuron-neuron junctions, or synapses, have been studied extensively, progress in understanding neuron-glia junctions has been comparatively slow. Nevertheless, neurons develop morphologically elaborate contacts with specialized glial partners. To identify the molecular machinery that governs neuron-glia junctions, we turned to a model organism renowned for its invariant anatomy and powerful genetics: the nematode Caenorhabditis elegans.
We focused on two sensory neurons, called URX and BAG. These neurons extend dendrites to the animal’s nose, where they terminate in membranous elaborations that wrap around thumb-like protrusions from a single glial cell (the IL socket). Using timelapse imaging, we show that URX and BAG dendrites form by retrograde extension, in which the nascent dendrite ending attaches to the nose early in development and dendrites are stretched to their full length during embryo elongation. When dendrites become detached from the nose, they fail to fully extend. We suggest that junctions with the glial cell anchor dendrite endings to the nose during embryogenesis.
In Chapters 2 and 3, we use forward genetic screens and candidate-based approaches to show that two cell adhesion molecules, SAX-7/L1CAM and HMR-1/Cadherin, and two scaffolding molecules, GRDN-1/CCDC88C and MAGI-1/Magi1, are required for BAG and URX dendrite morphogenesis. Rescue and cell-specific depletion experiments suggest that GRDN-1, MAGI-1, and HMR-1 can all act non-cell autonomously in glia to promote dendrite extension. SAX-7 can act cooperatively in both neurons and glia to drive dendrite development. In Chapter 4, we identify additional molecules required for dendrite formation, including AFD-1, which links cell junctions to the actin cytoskeleton. Interestingly, all five of these proteins are associated with epithelial cell junctions. Thus, to our surprise, we find that the URX- and BAG-glia junctions use junction components shared with epithelia. This suggests that the extensive knowledge of cell junctions from epithelial biology might be readily applied to understanding neuron-glia interactions.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37365139
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