Human brain development on a vacation island

The island of Capri, lying south of Naples and West of Sorrento, is an Italian vacation destination known for its exquisite views and extravagant luxury shopping. So, it may come as a surprise to think that this could also be an ideal location where science-based education on human brain development might occur. Well, for one week in October 2024, this was indeed the case as the European Molecular Biology Organization (EMBO) hosted a workshop titled “Unlocking human brain complexity using 3D culture and single cell omics.”

EMBO workshops are typically smaller conferences, with an attendance size of about 100 or so registrants, to provide a more intimate atmosphere that promotes close interaction among scientists. The exotic setting of the host site also offers a more relaxed environment to foster networking and encourage collaborative discussions between research groups.

This EMBO workshop in Capri did not disappoint, and it served as a “Who’s Who” in the cerebral organoid research field, touting a roster of distinguished speakers highlighted by Sergiu Pasca, Madeline Lancaster, Jurgen Knoblich, Barbara Treutlein, and Paola Arlotta — a Mount Rushmore worthy collection of scientists in the in vitro stem cell brain development field. 

The workshop started off with a bang, led by a plenary lecture from Paola Arlotta, Ph.D., Professor and Chair of Harvard University’s Department of Stem Cell & Regenerative Biology (HSCRB), who detailed her lab’s work on the use of multi-donor stem cell villages to generate chimeric organoids to investigate population-wide differences in brain development and susceptibility to disease-causing environmental agents https://www.nature.com/articles/s41586-024-07578-8.

Later, we heard from Barbara Treutlein, Ph.D., Principal Investigator at ETH Zurich, on her lab’s use of multi-omics platforms and computational analysis pipeline to study human brain development. Recently, her team and others in the field have collaborated to compile transcriptomic datasets from neural organoid protocols while cross-referencing against existing brain atlases to generate an integrated organoid cell atlas https://www.nature.com/articles/s41586-024-08172-8.

On the topic of neural organoids, we heard from Jurgen Knoblich, Ph.D., Professor of Synthetic Biology at the Medical University of Vienna and Scientific Director at IMBA, who presented a set of new protocols to generate diverse neural subtypes https://www.biorxiv.org/content/10.1101/2024.11.15.623576v1. Meanwhile, Madeline Lancaster, Ph.D., Professor at MRC Laboratory of Molecular Biology (UK), discussed the challenges with organoid reproducibility across biologically diverse human induced pluripotent stem cell lines (hiPSCs). 

Another interesting theme that came from the meeting was the dynamic use of growth factor morphogen signals, known to construct the developing nervous system, in these in vitro derived organoid models. Additional work from the Treutlein lab has used morphogenetic analysis using high content imaging https://www.biorxiv.org/content/10.1101/2023.08.21.553827v1, along with multiplexed omics assays https://www.biorxiv.org/content/10.1101/2024.02.08.579413v1, to profile this dynamic range of morphogen signaling that is both time and concentration dependent; as have others https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00378-3.

Additionally, we heard from different groups detailing the versatility of specific morphogens, such as FGF8, in patterning diverse regions of the brain from anterior-derived pallial subtypes https://elifesciences.org/articles/98096 to posterior-defined hindbrain derivatives like cerebellum https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00430-7.

Finally, not to be overshadowed, was the incredible (and futuristic) work from the lab of Sergiu Pasca, MD., Professor of Psychiatry and Director of the Stanford Brain Organogenesis program. Sergiu’s lab is arguably revolutionizing the stem cell field with his team’s pioneering work on organoid assemblies, coined ‘assembloids’ https://www.nature.com/articles/d41586-021-02628-x. Most recently, his lab has generated diverse assembloid models to recreate intricate connections between regional boundaries of the developing neural tube https://www.biorxiv.org/content/10.1101/2024.06.26.600229v1, ascending pathways in the CNS https://www.biorxiv.org/content/10.1101/2024.03.11.584539v1, and modeling unique circuits within the brain https://www.biorxiv.org/content/10.1101/2024.10.13.617729v1.

While you might think that all this fascinating science was the highlight of the conference, there were also several amazing extracurricular events such as free-periods to explore the island, evening dinners with the expert speakers, and a conference-ending gala featuring folk dancers, singers, and musicians playing traditional Neapolitan music.

So, the next time you find yourself vacationing on an island, either in Capri or elsewhere, imagine that a group of scientists could be congregating nearby to discuss the latest scientific discoveries on the development of our human brains.

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