Role of VPS37D in morphological and functional neuronal alterations in Williams Beuren Syndrome

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Williams Beuren Syndrome (WBS) is a rare disease which is caused by the loss of a small part of DNA. The loss of just a small piece of genetic information has a tremendous impact on the bodies of affected individuals. In fact, these people have cardiovascular problems (which is also a major cause of precocious death), impaired gastrointestinal function and neurological deficits. The brain of WBS individuals has caught the attention of neuroscientist for a long time, because people affected by WBS have a so called “cocktail party” personality, which simply means they are overtly friendly and hypersocial. This, of course, can be seen as a positive feature, especially when compared to autistic individuals, which have the opposite problem and possess impaired social skills and introvert personalities. However, behind this apparently good trait, individuals affected by WBS have many neurological deficits such as intellectual disabilities, delayed development and impaired cognitive function. Moreover, we know that WBS individuals also have reduced brain size and smaller neurons, which are the main cell of the brain. This could mean that anatomical and cellular alterations could be the cause or at least contribute to the neurological deficits of WBS. By creating mice, which have the same genetic loss of humans with WBS, we were able to learn many things about the genes that are lost. Among the genes that are lost, some of them have not been studied at all. One of the genes is called VPS37D and is involved in the regulation of the neuronal membrane, which basically defines how big and articulated a neuron is. To this day, not only do we not know precisely what the effect of VPS37D loss in WBS is, but we don’t even know what it does in general. The goal of our proposal is to show that VPS37D is important for the adequate function of neurons, and that its loss has important implications for people affected by WBS.