Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12202/1340
Title: Loss of cyclin A inhibition drives Drosophila R8 neurons into the cell cycle resulting in cytokinetic and axonal defects
Authors: Ruggiero, Robert Paulsen
Keywords: Genetics.
Developmental biology.
Neurosciences.
Issue Date: 2012
Publisher: ProQuest Dissertations & Theses
Citation: Source: Dissertation Abstracts International, Volume: 74-03(E), Section: B.;Advisors: Hannes Buelow.
Abstract: Permanent cell cycle arrest in neurons remains poorly understood. It has been hypothesized that cell cycle activity disrupts neuronal cell fate determination, or alternatively that cell cycle activity disrupts neuronal development. To discern between these hypotheses we investigated photoreceptor neuron development in Drosophila mutants lacking the cyclin dependent kinase inhibitor roughex (rux). We find that rux ads as an essential barrier to cell division in Drosophila R8 photoreceptors, the founding neuron of each unit eye. In rux null mutants, R8 specification occurred normally but endogenous Cyclin A/CDK activity drove these neurons into ectopic into mitosis. After mitosis R8 cells did not divide and remained binucleate syncytia, revealing that a second barrier to neuron division occurs at cytokinesis. In these cells daughter nuclei became mislocalized and migrated towards the axon tip, in a kinesin heavy chain dependent manner. Mutations in key Cyclin A regulators, APC1 and Cdh1, exhibited phenotypes similar to rux, indicating these defects represent a general condition resulting from mitotic activity in neurons. These observations explain previous mosaic analyses showing rux and Cdh1 are each essential in R8 cells for the formation of normal ommatidia. These data support the conclusion that cell cycle activity does not prevent neuronal fate specification, but disrupts the development of neurons.
URI: https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3532196
https://hdl.handle.net/20.500.12202/1340
Appears in Collections:Albert Einstein College of Medicine: Doctoral Dissertations

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.