Daam2 is required for dorsal patterning via modulation of canonical Wnt signaling in the developing spinal cord.
The Daam family of proteins consists of Daam1 and Daam2. Although Daam1 participates in noncanonical Wnt signaling during gastrulation, Daam2 function remains completely uncharacterized. Here we describe the role of Daam2 in canonical Wnt signal transduction during spinal cord development. Loss-of-function studies revealed that Daam2 is required for dorsal progenitor identities and canonical Wnt signaling. These phenotypes are rescued by β-catenin, demonstrating that Daam2 functions in dorsal patterning through the canonical Wnt pathway. Complementary gain-of-function studies demonstrate that Daam2 amplifies Wnt signaling by potentiating ligand activation. Biochemical examination found that Daam2 association with Dvl3 is required for Wnt activity and dorsal patterning. Moreover, Daam2 stabilizes Dvl3/Axin2 binding, resulting in enhanced intracellular assembly of Dvl3/Axin2 complexes. These studies demonstrate that Daam2 modulates the formation of Wnt receptor complexes, revealing new insight into the functional diversity of Daam proteins and how canonical Wnt signaling contributes to pattern formation in the developing spinal cord.
Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Hyun Kyoung
HK
Lee
Benjamin
B
Deneen
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D015153:Blotting, Western; D019521:Body Patterning; D019556:COS Cells; D002450:Cell Communication; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D002522:Chlorocebus aethiops; D000072261:Dishevelled Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D038081:Organogenesis; D010750:Phosphoproteins / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism*; D060449:Wnt Signaling Pathway
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; C000606585:Dvl3 protein, mouse; D008840:Microfilament Proteins; D010750:Phosphoproteins