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Title page for ETD etd-12012009-163833


Type of Document Dissertation
Author Moynihan, Katherine Lynn
URN etd-12012009-163833
Title Murine CENP-F regulates microtubule network function and is essential in heart development
Degree PhD
Department Cell and Development Biology
Advisory Committee
Advisor Name Title
Vivien Casagrande Committee Chair
David Bader Committee Member
Irina Kaverina Committee Member
Maureen Gannon Committee Member
Patricia Labosky Committee Member
Keywords
  • heart
  • centrosome
  • cell biology
  • developmental biology
  • CENP-F
  • microtubule
Date of Defense 2009-11-24
Availability unrestricted
Abstract
This project characterizes CENP-F protein function at a cellular and organ level. First, I outline our plan used to identify novel binding partners. The first binding partner I describe is syntaxin 4 and the interaction between CENP-F and this SNARE protein regulates vesicular transport along the microtubule network. Second, I discuss the binding of CENP-F and Hook2, a centrosomal protein, and the role of CENP-F in centrosomal microtubule nucleation. Additionally, novel immunohistochemical and gene ablation reagents were developed to complete these studies. These two binding partners both illustrate a vital role of CENP-F with the microtubule network throughout the cell. To introduce our model of organogenesis, I outline the process of heart development, with emphasis on the avian model. Given the dynamic and high expression of CENP-F in this vital organ, it is an excellent model in which to study the role of CENP-F in vivo. Finally, I report our initial findings with the heart-specific deletion of CENP-F in the mouse. The ablation of CENP-F in developing cardiomyocytes leads to a small heart with thinner walls that develops progressive dilated cardiomyopathy and irregular conduction patterns. Investigations into the underlying function that is disrupted the CENP-F-/- hearts resulting in these phenotypes are ongoing. Overall, this thesis characterizes the function of CENP-F via binding partner identification and disruption of protein function using cell biological methodologies and genetic deletion. These approaches elucidate function with the microtubule network in vesicular transport and centrosomal microtubule nucleation and show an important role in normal murine heart development.
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