Biomedical Engineering Reference
In-Depth Information
CHAPTER NINE
Dishevelled: In Vivo Roles of a
Multifunctional Gene Family
During Development
Anthony Wynshaw-Boris
1
UCSF School of Medicine, San Francisco, California, USA
1
Corresponding author: e-mail address: wynshawborist@peds.ucsf.edu
Contents
1. Canonical Wnt Pathway
215
2. PCP Pathway, a Noncanonical Wnt Pathway
217
3. Conserved Mammalian PCP Pathway
218
3.1 PCP pathway in inner ear development
218
3.2 PCP pathway in neurulation
219
3.3 PCP pathway in axonal tract development
220
3.4 PCP pathway during gastrulation: mouse prickle-1 (mpk1) is essential for
epiblast AB polarity
220
4.
Dvl Genes: Crossroads of Wnt and PCP Pathways
221
5. Single Mutants for Dvl Genes in the Mouse: Unique Phenotypes
221
6.
Dvl1
Null Mice: Social Interaction Defects
222
7.
Dvl2 Mutant Mice: Cardiac, Neurulation, and Skeletal Defects
224
8.
Dvl3
Mutant Mice
225
9.
Dvl Double Mutants: Redundancy Among the Dvl Genes
225
10.
Dvl1/2 Double Mutants
225
11.
Dvl1/3 Double Mutants
226
12.
Dvl2/3 Double Mutants
227
13.
Dvl1,2,3 Triple Mutants Display Defects in the Posterior Placement of Nodal Cilia
227
14.
Dvl Conditional Tagged Alleles
228
15.
Dvl Transgenes Demonstrate Functional Redundancy
229
16.
Dvl2 Allelic Series to Distinguish Wnt and PCP Pathway Phenotypes In Vivo
229
17. Conclusions and Future Studies
231
References
232
Abstract
Dishevelled proteins are highly conserved throughout evolution and participate in ca-
nonical and noncanonical Wnt pathways. In particular, Dvls participate in the planar cell
polarity (PCP) pathway that is important for a variety of developmental processes. There
are three Dvl genes in mammals. These three genes are highly conserved and broadly
