Form and fate: How shape influences human brain development and evolution

The human brain is what sets us apart as a species. It is therefore unique in many ways, but one of the most obvious distinguishing features is its size. Because size is determined by cellular makeup, we are interested in uncovering mechanisms that influence neural stem cell fate and thus determine how many and what types of neurons are generated. We use cerebral organoids generated from human and nonhuman ape pluripotent stem cells that exhibit the same cellular organization of the early fetal brain. These methods are allowing us to tackle questions previously impossible with more traditional approaches. Indeed, our recent findings provide insight into regulation of brain size and neuron number across species, identifying key stages of early neural stem cell expansion that set up a larger starting cell number to enable the production of increased numbers of neurons in humans. We are now exploring mechanisms controlling this timing, and how progenitors in the developing human cortex interpret their environment to tell what time it is in development. Overall, our findings are pointing to key, human-specific aspects of brain development and function, that have important implications for neurological disease.


Dr Madeline Lancaster is a Group Leader in the Cell Biology Division of the Medical Research Council Laboratory of Molecular Biology (LMB), part of the Cambridge Biomedical Campus in Cambridge, UK. Madeline joined the LMB in 2015, after completing a postdoctoral fellowship at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna, where she developed brain organoids.

Research in the Lancaster lab focuses on human brain development using stem cells to generate brain organoids that allow modelling of human brain development in vitro. The laboratory studies the most fundamental differences between human brain development and that of other mammalian species. The lab also studies cellular mechanisms underlying neurodevelopmental disorders such as autism and intellectual disability.

Madeline was awarded the 3Rs Prize by the National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs) in 2015 for her development of a 3D model of the embryonic human brain created from stem cells (brain organoids), which minimise the use of animals in medical research. She was awarded the International Society for Stem Cell Research (ISSCR) Dr Susan Lim Award for Outstanding Young Investigator and a Vallee Scholarship in 2021 and honoured as the Laureate for Life Sciences in the 2022 Blavatnik Award for Young Scientists in the UK.