Show simple item record

dc.contributor.advisorAckley, Brian
dc.contributor.authorHuarcaya Najarro, Elvis
dc.date.accessioned2013-02-17T16:37:06Z
dc.date.available2013-02-17T16:37:06Z
dc.date.issued2012-12-31
dc.date.submitted2012
dc.identifier.otherhttp://dissertations.umi.com/ku:12472
dc.identifier.urihttp://hdl.handle.net/1808/10816
dc.description.abstractCadherin proteins are cell adhesion molecules involved in multiple aspects of the development of the nervous system. A subgroup of these proteins, called protocadherin, has been recently shown to play key roles during the formation of neuronal networks in various animal models. In the model nematode Caenorhabditis elegans, there is only one protocadherin protein, called fmi-1, which has not being fully characterized. Here, I describe the cellular and molecular characterization of the cadherin fmi-1/flamingo in the development of the D-type GABAergic neurons. Mutant alleles for fmi-1 were originally isolated during a genetic screen looking for genes that regulate synaptic morphology in the D-type GABAergic neurons, which are comprised of DD and VD neurons. In fact, fmi-1 animals display synaptic defects, which include reduced synapse number and aberrant synapse size and morphology, as well as an abnormal accumulation of synaptic vesicles at non-synaptic regions. Electron microscopy data reinforce these observations. Although synaptic defects were present in both the ventral nerve cord (VNC) and the dorsal nerve cord (DNC), it appears that synapses corresponding to the VD neurons are primary affected by fmi-1 mutations. Furthermore, transcriptional analysis suggests that fmi-1 is not present in the VD neurons. In fact, expression of fmi-1 under a promoter that is not active in the VD neurons was able to partially rescue these defects. Therefore, in this cellular context, fmi-1 might be acting cell non-autonomously. Mutations in fmi-1 also cause neurite growth defects in the VD neurons along the anteroposterior (A/P) axis. I have developed a VD-specific marker to visualize and score these defects. VD neurons in fmi-1 animals display two different types of neurite defects. First, an anterior ventral neurite (AVN), which will become the axon, fails to extend fully in the VNC. Second, VD neurons display a posterior ventral neurite (PVN) instead of a normal anterior neurite, which causes commissure patterning defects along the anteroposterior axis (A/P axis). These defects arose during the early development of the VD neurons and they appear not to be caused by defects in cell division or cell fate specification. Fly and vertebrate homologues of fmi-1 can work as part of the planar cell polarity (PCP) pathway. We found that mutations in two core components of the PCP pathway, vang -1 and prkl-1, do not display fmi-1-like defects in the VD neurons. Therefore, fmi-1 might be working independently from the PCP pathway to regulate directional neurite growth in these neurons. Finally, I also describe genetic interactions between fmi-1 and two components of the Wnt pathway, lin-17/frizzled and dsh-1/disheveled. Epistasis analyses suggest that lin-17 and dsh-1 work in a pathway distinct from that of fmi-1 to regulate directional neurite growth in the VD neurons along the A/P axis. In summary, fmi-1 plays multiple roles during the development of the D-type GABAergic neurons. Interestingly, fmi-1 and the Wnt pathway work redundantly to regulate VD neurite growth along the A/P axis in the VNC in C. elegans.
dc.format.extent136 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsThis item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
dc.subjectNeurosciences
dc.subjectDevelopmental biology
dc.subjectAxon growth
dc.subjectCadherin
dc.subjectC. elegans
dc.subjectFlamingo
dc.subjectFmi-1
dc.subjectWnt
dc.titleThe role of the cadherin fmi-1/flamingo in the development of the D-type GABAergic neurons
dc.typeDissertation
dc.contributor.cmtememberAckley, Brian
dc.contributor.cmtememberKaranicolas, John
dc.contributor.cmtememberLundquist, Erik A.
dc.contributor.cmtememberMacDonald, Stuart J.
dc.contributor.cmtememberKelly, John
dc.contributor.cmtememberWard, Robert E.
dc.thesis.degreeDisciplineMolecular Biosciences
dc.thesis.degreeLevelPh.D.
kusw.oastatusna
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record