Amotl2a interacts with the Hippo effector Yap1 and the Wnt/β-catenin effector Lef1 to control tissue size in zebrafish

摘要

How do organs and tissues know when to stop growing? A cell communication pathway known as Hippo signaling plays a central role as it can tell cells to stop dividing. It is activated when cells in developing tissues come into contact with each other and causes a protein called Yap1 to be modified, which prevents it from entering the cell nucleus to activate genes that are involved in cell division. In a zebrafish embryo, an organ called the lateral line forms from a cluster of cells that migrate along the embryo's length. At regular intervals, the cluster deposits small bunches of cells from its trailing end. The resulting loss of cells from the cluster is balanced by cell division at the front of the cluster, which is triggered by another signaling pathway called Wnt signaling. A protein of the ‘Motin’ family called Amotl2a is present in this migrating cluster. Motin proteins form junctions between cells and inhibit the activity of Yap1, but it is not known whether they are involved in regulating the size of organs. Here, Agarwala et al. used the lateral line as a model to study the control of organ size in zebrafish embryos. The experiments show that when Amotl2a is absent, the migrating cell cluster becomes larger, with the highest levels of cell division occurring at its trailing end. Yap1 and a protein involved in Wnt signaling called Lef1 are also present in the cluster and are required for it to be normal in size. In zebrafish that lack Amotl2a, the additional loss of Yap1 prevents this cluster from becoming too large. From these and other results, it appears that Amotl2a regulates the size of the lateral line cell cluster by restricting the ability of Yap1 and Lef1 to promote cell division. Agarwala et al.'s findings demonstrate a role for Amotl2a in controlling the size of organs. A future challenge is to understand the details of how it restricts the activities of Yap1 and Lef1.