Research

 Our central question is: How does the genome build the brain?

We explore this by investigating:

• Cellular Fate Specification: How do early genetic instructions determine the diverse cell types in the brain?

• Neuronal Circuit Formation: What mechanisms ensure that neurons connect precisely, and how do these connections affect behavior?

Our studies use both Drosophila (fruit fly) and mammalian models to uncover the principles behind neural development. The findings not only advance our basic scientific knowledge but also have implications for understanding human neurological disorders. The central question of the lab’s research is: how does the genome build the brain to be functional and resilient? A complex functional biological system is the emergent property of the self-organizing capacity of molecular networks. The most fundamental of these networks is the genome. The most sophisticated is the brain. The genomic network produces a set of instructions that builds the neuronal network to be functional over a lifetime and to be resilient and robust. We try to understand what that set of instructions is. Yet sometimes this network succumbs to disease and degeneration. Why? Our work tries to understand how developmental mechanisms lead to resilience and how defects in them predispose to degeneration. In total, our work has resulted in over 100 publications contributing important insights into these questions.

At one end during developmental time, there is cell fate specification. At the other end, there is the formation of precise neuronal connections. Because each neuron is characterized by specific connections, the two features must be linked. Over the past decade, we have made major contributions to understanding these questions. We have unraveled the gene regulatory basis of cell fate specification in the fly retina (Aerts et al., 2009, 2010; Quan et al., 2016; Ramaekers et al., 2019) and the fly and mouse brain (Mora et al., 2018; Zhang et al., 2021). On the other hand, we began a long-term effort towards understanding the mechanisms that regulate the specificity, variability, and robustness of brain wiring. Our data clearly show that wiring the brain is a more complex and plastic process than has been appreciated in studies using the fly PNS as a model. We have concentrated on how single neurons integrate various attractive and repulsive signals during brain wiring, and how they interact with one another to make wiring choices (Srahna et al., 2006; Langen et al., 2013; Zschaetzsch et al., 2014; Oliva et al., 2016, Dutta et al., 2023; Andriatsilavo et al., 2025) and how that influences behavioral individuality (Linneweber et al., 2020; Bengochea et al., 2023). Many genes that regulate brain wiring are associated with human disease. We have unraveled the roles of the Drosophila homologues of the Fragile X protein (Morales et al., 2002; Reeve et al., 2005, 2008; Okray et al., 2015; Franco et al., 2017) and the Amyloid Precursor Protein in axonal growth and guidance (Leyssen et al., 2005; Soldano et al., 2013, Liu et al., 2021), neuro-glial communication (Kessissoglu et al., 2020) and human specific features of cortical neurogenesis (Shabani et al., 2023). 

If you're interetsed in learning more, please navigate to our publications page and read the papers that interest you.