How do you make a nervous system that works… and keep it that way?
Diversity is a beautiful thing and unity is a powerful thing. Put them together, and what do you get? You get the most beautiful and powerful of all things: evolution! Much like human beings, cells of the nervous system are exquisitely diverse. They have diverse shapes and perform diverse functions. Yet, also like humans, underneath this bewildering diversity lies a profound unity: the genome. How can exactly the same genome produce so many different cells? The answer is that it depends on how a cell interprets its genome. Different cells extract differential information from their genomes, using transcription factors that activate or repress different genes. Our lab is interested in understanding the contribution of the information encoded by cell type specific transcription factors to cell fate specification. For this, we use the development and evolution of sensory organs - the eye, ear and nose - in the fruit fly Drosophila melanogaster as a model system. We compare the genetic programs of different sensor cells within one species, as well as the genetic programs of the same sensory organs across different Drosophila species. In this way we hope to learn about the rules of cellular diversity and specialization. Because cellular specialization goes wrong in cancer, these findings have profound implications for human health.
Making a brand new specialized nervous system cell is just the beginning. Now it has to grow axons and dendrites and begin its journey. Axons of young brain neurons have a promiscuous wanderlust! They like to travel, explore new environments, search for suitable partners and establish as many connections as they can. They cannot help it. It’s an irresistible drive.- it’s in their genes, you could say! After a certain age, however, they settle down, and, satisfied with the extensive network of connections they have made, stop searching for new ones. They devote their lives to their jobs, and generally perform exceptionally well, given the monumental task they have: making the formidable machine that is the organism live, behave and reproduce. This dedication however, comes at a price: the loss of their youthful sense of wanderlust. If their connections are cut, they are unable to get themselves to travel, make new connections and start all over again. Using the mighty fruit fly as a model organism, we study the genes that allow young axons to grow and establish connections. We also ask why the same axons, now older and wiser, are unable to grow again and re-establish lost connections if they are injured or struck down by disease.
We combine powerful molecular genetic tools, innovative whole-brain culture approaches and high-resolution imaging to search for genes and gene ensembles that control axonal growth during development. We also ask if the same genes might help injured or diseased axons to regenerate and survive.
Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates NeurogenesisQuan X, Yuan L, Tiberi L, Claeys A, De Geest N, Yan J, van der Kant R, Xie W, Klisch T, Schymkowitz J, Rousseau F, Bollen M, Beullens M, Zoghbi H, Vanderhaeghen P, Hassan BCELL, 164, 460-75, 2016 A novel fragile X syndrome mutation reveals a conserved role for the carboxy-terminus in FMRP localization and functionOkray Z, De Esch C, Van Esch H, Devriendt K, Claeys A, Yan J, Verbeeck J, Froyen G, Willemsen R, De Vrij F, Hassan BEMBO Molecular Medicine, 7, 423-37, 2015 The Drosophila Homologue of the Amyloid Precursor Protein Is a Conserved Modulator of Wnt PCP SignalingSoldano A, Okray Z, Janovska P, Tmejová K, Reynaud E, Claeys A, Yan J, Atak Z, De Strooper B, Dura J, Bryja V, Hassan BPLOS BIOLOGY, 11, e1001562, 2013 Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in DrosophilaLangen M, Koch M, Yan J, De Geest N, Erfurth M, Pfeiffer B, Schmucker D, Moreau Y, Hassan BeLife, 2, e00337, 2013
14/06/2016 - Our senses of smell and taste are particularly important for survival: they allow us to know if some food is potentially tainted, poisoned, or expired, thanks to sensory neurons. Are these protection mechanisms also present in animals?
28/01/2016 - A mechanism, found by Bassem Hassan's team, is a simple reversible chemical modification, critical for the production of sufficient number of neurons, their differentiation and the development of the nervous system.
24/05/2013 - Alessia Soldano and Bassem Hassan (VIB/KU Leuven) were the first to unravel the function of APPL – the fruit-fly version of APP – in the brain of healthy fruit flies.
12/11/2010 - VIB researchers attached to the K.U.Leuven have improved the fruit fly as a model for studying the connections between brain cells.
23/02/2009 - Starting with the tiny fruit fly, and then moving into mouse and human patients, researchers at VIB showed that the same gene suppresses cancer in all three. Reciprocally, switching off the gene leads to cancer.
02/06/2008 - Microsurgery on the brain of the fruit fly leads to new insights into irreparable nerve injuries
11/10/2006 - Scientists from VIB connected to the Katholieke Universiteit Leuven, led by Bassem Hassan, have achieved a major step in unraveling the growth process of axons
08/05/2006 - Researchers from VIB connected to the Catholic University of Leuven have now developed ENDEAVOUR: a computer program that compiles and processes data from a variety of databases and identifies the genes that play a key role in the origin of a disorder