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 - as well as the visual areas of the brain the fruit fly Drosophila melanogaster as one 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. We also ask whether similar rules and mchanisms apply in the mammlaina brain using the mouse cerebellum and human iPS cells as model systems.

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.

Selected publications

  1. Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis
    Quan XJ, Yuan L, Tiberi L, Claeys A, De Geest N, Yan J, van der Kant R, Xie WR, Klisch TJ, Shymkowitz J, Rousseau F, Bollen M, Beullens M, Zoghbi HY, Vanderhaeghen P, Hassan B
    CELL, 164, 460-75, 2016

  2. Beyond Molecular Codes: Simple Rules to Wire Complex Brains
    Hassan B, Hiesinger P
    CELL, 163, 285-91, 2015

  3. The Drosophila Homologue of the Amyloid Precursor Protein Is a Conserved Modulator of Wnt PCP Signaling
    Soldano A, Okray Z, Janovska P, Tmejová K, Reynaud E, Claeys A, Yan J, Atak Z, De Strooper B, Dura J, Bryja V, Hassan B
    PLOS BIOLOGY, 11, e1001562, 2013

  4. Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
    Langen M, Koch M, Yan J, De Geest N, Erfurth M, Pfeiffer B, Schmucker D, Moreau Y, Hassan B
    eLife, 2, e00337, 2013

  5. Conditional mutagenesis in Drosophila
    Choi C, Vilain S, Langen M, Van Kelst S, De Geest N, Yan J, Verstreken P, Hassan B
    SCIENCE, 324, 54, 2009

  6. Evolution of neural precursor selection: functional divergence of proneural proteins
    Quan XJ, Denayer T, Yan J, Jafar-Nejad H, Philippi A, Lichtarge O, Vleminckx K, Hassan B
    Development, 131, 1679-89, 2004

  7. Drosophila fragile X protein, DFXR, regulates neuronal morphology and function in the brain
    Morales J, Hiesinger PR, Schroeder AJ, Kume K, Verstreken P, Jackson FR, Nelson DL, Hassan B
    Neuron, 34, 961-72, 2002