The Roles of Arl13b in Cilia, Cell Signaling, and Embryonic Development Open Access

Larkins, Christine Elizabeth (2011)

Permanent URL:


The Roles of Arl13b in Cilia, Cell Signaling, and Embryonic Development
By Christine E Larkins
Cilia are antennae-like projections that are found on the apical surface of most
vertebrate cells. They were discovered almost a century ago, but their significance in
multiple cellular events is only beginning to be understood. Cilia were initially
recognized for their roles in creating motility, however, more recently it was found that
non-motile primary cilia are required for various cell signaling events such as signaling
pathway integrity, mechanosensation, and even light detection in photoreceptor cells.
Mutations in ciliary proteins can lead to a variety of human syndromes called
ciliopathies. Left-right axis defects are common symptoms in ciliopathies because axis
establishment in the embryo requires both motile and primary cilia, but the functions of
primary cilia in the process are less understood. Other common symptoms, such as
polydactyly, result from defects in the Sonic Hedgehog (Shh) signaling pathway. Almost
all components of the Shh signaling pathway localize to the cilium which is required for
pathway integrity. However, it is not clear how Shh signaling proteins interact within the
cilium or why cilia are required for pathway integrity. Taken together, a better
understanding of cilia protein function and their roles in embryonic development and
signaling events is required for grasping the etiology of ciliopathies.
This dissertation focuses on understanding the function of the cilia protein
Arl13b, which is mutated in the ciliopathy Joubert Syndrome. Loss of Arl13b leads to
shortened cilia with a defect in cilia ultrastructure, although the precise function of
Arl13b in cilia is not clear. Mouse mutants lacking Arl13b, Arl13bhennin, have both left-
right axis and Shh signaling defects. This dissertation examines the defects in
establishing the left-right axis in Arl13bhennin mutant embryos and investigates the
function of Arl13b in ciliogenesis and Shh signaling. Through examining these processes
I have found that Arl13b is important for maintaining proper levels of ciliary
components, which is important for both Shh signaling and cilia structure, and I have
shown that Arl13b may have additional roles outside of the cilium that are required for
left-right axis establishment.

The Roles of Arl13b in Cilia, Cell Signaling, and Embryonic Development
Christine E Larkins
B.S., College of Charleston, 2005
Advisor: Tamara Caspary
A dissertation submitted to the Faculty of the
James T. Laney School of Graduate Studies of Emory University
in partial fulfillment of the requirements for the degree of
Doctor of Philosophy
in Biochemistry Cell and Developmental Biology

Table of Contents

Chapter 1: Cilia, Signaling, and Embryonic Development 1
1.1 The Significance of Cilia 2
1.2 Cilia Structure, Building Cilia, and Intraflagellar Transport 3
1.3 Targeting, Transport, and Entry to the Cilium

1.4 Cilia in Left-Right Axis Specification
1.5 Shh Signaling and Cilia

1.6 Arl13b Function in Cilia and Shh Signaling

Chapter 2: Materials and Methods

Chapter 3: The Cilia Protein Arl13b is Required for Efficient Nodal Signaling
Activity During Left-Right Axis Specification in Mouse

3.1 Summary

3.2 Introduction

3.3 Results

3.4 Discussion

Chapter 4: Arl13b Regulates Ciliogenesis and the Dynamic Localization of
Shh Signaling Proteins


4.1 Summary

4.2 Introduction

4.3 Results

4.4 Discussion

Chapter 5: Models of Arl13b Function


5.1 Arl13b in Nodal Signaling


About this Dissertation

Rights statement
  • Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.
Subfield / Discipline
  • English
Research Field
Committee Chair / Thesis Advisor
Committee Members
Last modified

Primary PDF

Supplemental Files