Polarity regulation is conserved in flies and mice
Planar cell polarity is a fundamental process during development, coordinating the alignment of neighboring cells within the plane of a tissue. A Human Frontier Science Program grant team from the USA, Israel and Japan, along with collaborators from Fudan University in China, has demonstrated a conserved role for Ankrd6 in regulating planar cell polarity in both the fruit fly and mouse.
HFSP Program Grant holders Karen Avraham, Ping Chen, Fumio Matsuzaki and David Sprinzak and colleaguesauthored on Thu, 20 November 2014
During the development of an embryo, cells need to line up in an organized pattern in order to form different parts of the body, including the brain and ear. This process, named planar cell polarity (PCP), is a common developmental process required for generating an elongated body from a single fertilized egg in vertebrates, the formation of a closed spinal cord and brain, and the normal formation and function of many other tissues, including the inner ear.
Figure: Three rows of sensory hair cells of the mouse inner ear are labeled with antibodies. Myosin VI labels the cytoplasm (red), phalloidin labels the actin in the stereocilia (green) and acetylated tubulin labels the kinocilium (blue). Along the bottom, paint fill preparations of the developing inner ear from embryonic day 10 through postnatal day 17.5 of the mouse.
HFSP grant team members, Ping Chen from the USA, Karen Avraham and David Sprinzak from Israel and Fumio Matsuzaki from Japan together with the Chi team from Fudan University, have demonstrated that over-expression of the murine Ankrd6 (mAnkrd6) gene, which shares homology with the Drosophila PCP gene diego, causes a typical PCP phenotype in Drosophila and can rescue the loss of function of diego in Drosophila. In mice, mAnkrd6 protein displays asymmetric membrane localization in cells of the inner ear sensory organs, characteristic of a membrane-associated PCP protein. The loss of mAnkrd6 leads to PCP defects in the inner ear sensory organs. Moreover, elicited canonical Wnt signaling is significantly increased in mouse embryonic fibroblasts from mAnkrd6 knockout mice in comparison to wild-type controls.
Together, these results indicate that mAnkrd6 is a functional homolog of the Drosophila diego gene for mammalian PCP regulation and could act to suppress canonical Wnt signaling. This work provides a key role for Ankrd6 in forming the pattern required for proper development of the ear.
The study is featured on the cover of the November 1, 2014 issue of Developmental Biology.
Ankrd6 is a mammalian functional homolog of Drosophila planar cell polarity gene diego and regulates coordinated cellular orientation in the mouse inner ear. Jones C, Qian D, Kim SM, Li S, Ren D, Knapp L, Sprinzak D, Avraham KB, Matsuzaki F, Chi F, Chen P. (2014) Dev. Biol. 395:62-72.