Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development

• DOI: 10.1038/srep20727
• Publication Date: 2016-02-17T10:35:59Z
• Authors: Sohinee Bhattacha...; Mark A Rainey; Priyanka Arya; Bhopal C. Mohapatra; Insha Mushtaq; Samikshan Dutta; Manju George; Matthew D. Storck; Rodney D. McComb; David Muirhead; Gordon L. Todd; Karen Gould; Kaustubh Datta; Janee Gelineau-va...; Vimla Band; Hamid Band
• Keywords: Smoothened

Abstract Members of the four-member C-terminal EPS15-Homology Domain-containing (EHD) protein family play crucial roles in endocytic recycling cell surface receptors from endosomes to plasma membrane. In this study, we show that Ehd1 gene knockout mice on a predominantly B6 background is embryonic lethal. -null embryos die at mid-gestation with failure complete key developmental processes including neural tube closure, axial turning and patterning tube. We found display short stubby cilia developing neuroepithelium day 9.5 (E9.5). Loss EHD1 also deregulates ciliary SHH signaling displaying features indicative increased signaling, significant downregulation formation GLI3 repressor increase ventral neuronal markers specified by SHH. Using MEFS co-localizes receptor Smoothened primary upon ligand stimulation. Under same conditions, was shown co-traffic into identify as direct binding partner Smoothened. Overall, our studies regulator novel cilium-associated trafficking Hedgehog signaling.