Disheveled mediated planar cell polarity signaling is required in the second heart field lineage for outflow tract morphogenesis
| Autor: | Bing Wang, Tanvi Sinha, Anthony Wynshaw-Boris, Sylvia M. Evans, Jianbo Wang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Chromosomes
Artificial Bacterial Dishevelled Proteins Morphogenesis Second heart field Nerve Tissue Proteins Biology Real-Time Polymerase Chain Reaction Wnt-5a Protein Article Heart development Polymerization Mice 03 medical and health sciences 0302 clinical medicine Cell polarity Animals Transgenes Outflow tract Molecular Biology In Situ Hybridization Actin Adaptor Proteins Signal Transducing DNA Primers 030304 developmental biology 0303 health sciences Lateral plate mesoderm Wnt signaling pathway Cell Polarity Neural crest Heart Cell Biology Phosphoproteins Planar cell polarity Immunohistochemistry Molecular biology Actins Outflow tract morphogenesis Cell biology Wnt Proteins Mutagenesis Signal transduction 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Developmental Biology. 370(1):135-144 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2012.07.023 |
| Popis: | Disheveled (Dvl) is a key regulator of both the canonical Wnt and the planar cell polarity (PCP) pathway. Previous genetic studies in mice indicated that outflow tract (OFT) formation requires Dvl1 and 2, but it was unclear which pathway was involved and whether Dvl1/2-mediated signaling was required in the second heart field (SHF) or the cardiac neural crest (CNC) lineage, both of which are critical for OFT development. In this study, we used Dvl1/2 null mice and a set of Dvl2 BAC transgenes that function in a pathway-specific fashion to demonstrate that Dvl1/2-mediated PCP signaling is essential for OFT formation. Lineage-specific gene-ablation further indicated that Dvl1/2 function is dispensable in the CNC, but required in the SHF for OFT lengthening to promote cardiac looping. Mutating the core PCP gene Vangl2 and non-canonical Wnt gene Wnt5a recapitulated the OFT morphogenesis defects observed in Dvl1/2 mutants. Consistent with genetic interaction studies suggesting that Wnt5a signals through the PCP pathway, Dvl1/2 and Wnt5a mutants display aberrant cell packing and defective actin polymerization and filopodia formation specifically in SHF cells in the caudal splanchnic mesoderm (SpM), where Wnt5a and Dvl2 are co-expressed specifically. Our results reveal a critical role of PCP signaling in the SHF during early OFT lengthening and cardiac looping and suggest that a Wnt5a→ Dvl PCP signaling cascade may regulate actin polymerization and protrusive cell behavior in the caudal SpM to promote SHF deployment, OFT lengthening and cardiac looping. |
| Databáze: | OpenAIRE |
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