Transcriptional and Epigenetic Regulation of Craniofacial Development (Filippo Rijli)

In this episode of the Epigenetics Podcast, we talked with Filippo Rijli from the Friedrich Miescher Institute about his work on transcriptional and epigenetic regulation of craniofacial and neuronal development. Dr. Rijli recalls pivotal moments in his career, including his postdoctoral work where he explored the functions of HoxA2 in craniofacial development. We discuss key findings from his landmark papers, highlighting how individual transcription factors like HoxA2 can dictate the topographic organization of neuronal circuits. His exploration of the whisker-to-barrel cortex circuit in mice unveils how sensory inputs are mapped and processed through precise neuronal connections. This intricate mapping reveals how singular genes can impact the wiring of entire neurological systems. We also reflect on the evolution of scientific communication throughout Filippo’s career, from the reliance on faxes and handwritten requests for paper reprints to today's instant access to research through digital platforms. His early experiences have instilled in him a resourcefulness that continues to inform his approach to research, particularly in environments with limited resources where collaboration becomes essential. Our discussion shifts to his recent research endeavors that delve into transcriptional and epigenetic regulation during neuronal and craniofacial development. Dr. Rijli elaborates on a 2015 study which demonstrated how the ectopic expression of HoxA2 could lead to the creation of artificial whisker maps in the brain, providing insights into how transcription factors guide neuronal behavior and circuit formation. His work on the histone methyltransferase EZH2 reveals its crucial role in the tangential migration of cerebellar neurons and the mechanisms that ensure these neurons reach their accurate destinations during development. Dr. Rijli's research further investigates the chromatin landscape of cranial neural crest cells, uncovering how polycomb group proteins maintain a poised state that enables these cells to respond flexibly to environmental signals. This concept of plasticity is particularly relevant in his latest research on nasal chondrocytes, suggesting that these cells retain developmental potential that may be harnessed in regenerative medicine. The discussions hint at a future where understanding these intricate mechanisms could lead to groundbreaking advancements in treating injuries or diseases. Throughout the episode, Dr. Rijli’s enthusiasm for discovery is palpable as he shares how each research finding leads to more questions, showcasing the iterative nature of scientific research. This dialogue provides not only a deep dive into his specific studies but also a broader view of how developmental biology continues to evolve, emphasizing the importance of understanding the molecular underpinnings of cellular identity and connectivity. References Oury, F., Murakami, Y., Renaud, J. S., Pasqualetti, M., Charnay, P., Ren, S. Y., & Rijli, F. M. (2006). Hoxa2- and rhombomere-dependent development of the mouse facial somatosensory map. Science (New York, N.Y.), 313(5792), 1408–1413. https://doi.org/10.1126/science.1130042 Di Meglio, T., Kratochwil, C. F., Vilain, N., Loche, A., Vitobello, A., Yonehara, K., Hrycaj, S. M., Roska, B., Peters, A. H., Eichmann, A., Wellik, D., Ducret, S., & Rijli, F. M. (2013). Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons. Science (New York, N.Y.), 339(6116), 204–207. https://doi.org/10.1126/science.1229326 Minoux, M., Holwerda, S., Vitobello, A., Kitazawa, T., Kohler, H., Stadler, M. B., & Rijli, F. M. (2017). Gene bivalency at Polycomb domains regulates cranial neural crest positional identity. Science (New York, N.Y.), 355(6332), eaal2913. https://doi.org/10.1126/science.aal2913 Kessler, S., Minoux, M., Joshi, O., Ben Zouari, Y., Ducret, S., Ross, F., Vilain, N., Salvi, A., Wolff, J., Kohler, H., Stadler, M. B., & Rijli, F. M. (2023). A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest. Nature communications, 14(1), 3242. https://doi.org/10.1038/s41467-023-38953-0 Related Episodes Chromatin Modifiers and Their Roles in Brain Development (Fides Zenk) Exploring DNA Methylation and TET Enzymes in Early Development (Petra Hajkova) The Role of H3K4me3 in Embryonic Deve