Cytoneme-mediated cell-cell contacts for Hedgehog reception

When an embryo develops, it is critical that tissues and organs form properly and at the right time. For this, cells need to be able to communicate over long distances by using signalling molecules called morphogens. Morphogens disperse via extensions that protrude from the surface of a ‘source’ cell. Previous research has shown that these extensions called cytonemes can transport the morphogens to ‘receiver’ cells, and depending on the distance from the source, build a concentration gradient that will either be higher or lower. These gradients then help unspecialized cells to develop into different specialized ones. One of the key morphogens during the development is the Hedgehog protein. Researchers have previously shown that vesicles along cytonemes of cells that produce Hedgehog transport the morphogen to the receiver cells. However, until now it was unclear how the Hedgehog signals are transferred and received. Here, Gonzalez-Mendez et al. – including researchers involved in the previous studies – investigated the cytonemes located on Hedgehog-receiving cells in the fruit fly. The results showed that these cytonemes are oriented towards the Hedgehog-producing cells and help to create a concentration gradient by varying their length. Moreover, the cytonemes from signal-producing and signal-receiving cells connect at specific sites that are distributed along their lengths. This suggests that the contact sites might help to transfer and receive the morphogens. Thus, the way cells communicate in other tissues of the body could be similar to how nerve cells communicate with each other in the brain. Our next challenges will be to fully understand how cytonemes transfer the Hedgehog signal. This could shed more light on how Hedgehog signaling can be controlled and modulated.