Ciliary Function in Mammalian Development

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ISBN: 9780123744531 | 0123744539
Cover: Hardcover
Copyright: 12/11/2008

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Cilia-the tiny hair-like structures on the surface of cells-have recently been identified as playing a role in a variety of disease and developmental disorders. Absent or defective cilia in certain cells can cause infertility, blindness, kidney disease, and lung disease. This volume presents recent findings in cilia research and current thought on the role of cilia in disease and developmental abnormalities.

Contributors	p. xi
Preface	p. xv
Basal Bodies: Platforms for Building Cilia	p. 1
Introduction	p. 2
Basal Body Architecture and Assembly	p. 3
Basal Body Functions in Ciliogenesis	p. 7
Approaches to the Study of Basal Bodies	p. 14
Conclusions	p. 17
References	p. 17
Intraflagellar Transport (IFT): Role in Ciliary Assembly, Resorption and Signalling	p. 23
Introduction	p. 24
Early Events in Ciliogenesis	p. 28
General Description of Intraflagellar Transport	p. 29
Discovery and Evolution of IFT	p. 30
The Canonical Anterograde IFT Motor	p. 32
Additional Kinesin Motors Involved in Ciliogenesis	p. 35
The Retrograde IFT Motor	p. 37
IFT Particle Polypeptides	p. 38
Functional Analysis of IFT Particle Polypeptides: Distinct Roles of IFT Complexes A and B	p. 39
Regulation of IFT	p. 41
Targeting of Proteins to the Ciliary Compartment: Clues from Ciliary Disease Genes	p. 43
IFT and Cilia-Mediated Signaling	p. 47
Conclusions and Perspectives	p. 49
Acknowledgments	p. 50
References	p. 50
How Did the Cilium Evolve?	p. 63
Introduction	p. 64
The Link Between Ciliary Evolution and Eukaryotic Divergence	p. 66
Hypotheses of the Origin of Cilia	p. 67
The Viral Hypothesis of Ciliary Origin	p. 68
The Autogenous Model for the Origin of Cilia	p. 71
Origin of Intraflagellar Transport and the Sensory Function of Cilia	p. 76
The Evolution of Ciliary Motility	p. 78
Acknowledgments	p. 79
References	p. 79
Ciliary Tubulin and Its and Post-Translational Modifications	p. 83
Introduction	p. 83
Production and Turnover of Ciliary Tubulin	p. 84
Post-Translational Modifications of Tubulin	p. 89
Conclusions	p. 103
Acknowledgments	p. 103
References	p. 104
Targeting Proteins to the Ciliary Membrane	p. 115
Introduction	p. 116
Structure of the Ciliary Membrane	p. 118
Functions of the Ciliary Membrane	p. 121
Protein Machinery Involved in Trafficking to the Ciliary Membrane	p. 127
Ciliary Targeting Sequences	p. 134
References	p. 139
Cilia: Multifunctional Organelles at the Center of Vertebrate Left-Right Asymmetry	p. 151
Introduction	p. 152
Vertebrate LR Asymmetry is Chiral Asymmetry	p. 154
The Structure and Distribution of Cilia in the Vertebrate Embryo	p. 155
Motile Primary Cilia in LR Development	p. 156
Mouse and Human Mutations Affecting Cilia Have a Wide-Ranging Effect on Left-Right and Cardiac Development	p. 158
A Structure with Prominent Primary Cilia is Essential to the Development of LR Asymmetry in Most Vertebrates	p. 160
Cilia at the LR Organizer Generate Directional Fluid Flow	p. 162
A Conserved Asymmetric Calcium Signal Is Found at the LR Organizer	p. 164
Do Cilia Lie at the Root of All Vertebrate LR Asymmetry, and What Leads from Asymmetric Calcium to Asymmetric Organogenesis?	p. 168
References	p. 169
Ciliary Function and Wnt Signal Modulation	p. 175
Introduction	p. 176
Overview of Wnt Signaling	p. 176
Emerging Roles of the Primary Cilium and Basal Body in Wnt Signaling Modulation	p. 179
Wnt and Ciliogenesis	p. 184
Wnt Dysfunction and Ciliopathy Phenotypes	p. 185
What Drives the Phenotype: Gain of Canonical Wnt Signaling or Loss of Noncanonical Wnt Signaling?	p. 185
Other Phenotypes	p. 187
Discussion	p. 189
Acknowledgments	p. 190
References	p. 191
Primary Cilia in Planar Cell Polarity Regulation of the Inner Ear	p. 197
Introduction	p. 198
Planar Cell Polarity and Ciliogenesis of the Inner Ear Sensory Organs	p. 200
Planar Cell Polarity Regulation for the Development of the Inner Ear	p. 206
Cilia and PCP Regulation	p. 209
Cilia and Determination of the Intrinsic Cellular Polarity of Inner Ear Cells	p. 214
Conclusions and Perspectives	p. 217
References	p. 219
The Primary Cilium: At the Crossroads of Mammalian Hedgehog Signaling	p. 225
Hh Signals Pattern Diverse Developing Tissues	p. 226
Hh Signal Transduction: Activating an Activator and Repressing a Repressor	p. 229
Functions of Gli Proteins in Development	p. 233
Defective Intraflagellar Transport Disrupts Mammalian Hh Signaling	p. 236
The Primary Cilium as a Cellular Signaling Center	p. 239
Mammalian Smo Activates the Hh Pathway at the Primary Cilium	p. 241
Proper Ciliary Function is Required for Processing of Gli Proteins	p. 242
Additional Ciliary Components Function in Hh Signal Transduction	p. 243
Are Cilia Involved in Hh Pathway-Mediated Tumorigenesis?	p. 246
Lingering Questions	p. 248
Acknowledgments	p. 249
References	p. 249
The Primary Cilium Coordinates Signaling Pathways in Cell Cycle Control and Migration During Development and Tissue Repair	p. 261
Introduction	p. 262
Cell Cycle Entry Regulated by PDGFR[alpha alpha] Signaling in the Primary Cilium	p. 267
Directional Cell Migration is Regulated by PDGFR[alpha] in the Primary Cilium	p. 272
The Extracellular Matrix and the Primary Cilium	p. 280
Polarization, Cell Migration, Cell Cycle Control and Wnt Signaling in the Primary Cilium	p. 282
Conclusions and Perspectives	p. 286
Acknowledgments	p. 288
References	p. 288
Cilia Involvement in Patterning and Maintenance of the Skeleton	p. 303
Introduction	p. 304
Cilia are Required for Anterior-Posterior Limb Patterning	p. 305
A Role for IFT/Primary Cilia in Endochondral Bone Formation and Development of the Postnatal Growth Plate	p. 312
Primary Cilia in Articular Cartilage	p. 318
A Role for Primary Cilia in the Development of the Bone Collar	p. 319
Primary Cilia in the Maintenance of Bone	p. 321
Primary Cilia in Craniofacial Development	p. 323
Primary Cilia in Tooth Development	p. 325
Summary	p. 326
Acknowledgments	p. 327
References	p. 327
Olfactory Cilia: Our Direct Neuronal Connection to the External World	p. 333
Olfaction as a Sensory Modality	p. 334
Anatomy and Organization of the Olfactory Epithelium	p. 335
Structure of Olfactory Cilia	p. 338
Formation of Olfactory Cilia	p. 344
Intraflagellar Transport	p. 347
Ciliary Proteome	p. 349
Olfactory Cilia and Disease	p. 355
Summary	p. 358
References	p. 359
Ciliary Dysfunction in Developmental Abnormalities and Diseases	p. 371
Introduction	p. 372
The Oak Ridge Polycystic Kidney (Orpk) Mouse: A Model For Human Ciliopathies	p. 374
Functions and Phenotypes Associated with Abnormal Motile Cilia	p. 376
Functions and Diseases Associated with Immotile Cilium	p. 383
Oligogenic Inheritance and Clinical Variability in the Ciliopathies	p. 409
Cilia Proteome and Genome Databases and the Identification of Human Ciliopathy Genes	p. 410
Acknowledgments	p. 412
References	p. 413
Index	p. 429
Contents of Previous Volumes	p. 437
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