Evolutionary biology of human and great ape brain development in cerebral organoids

Title	Evolutionary biology of human and great ape brain development in cerebral organoids
Acronym	CerebralHominoids
Website	http://www2.mrc-lmb.cam.ac.uk/group-leaders/h-to-m/madeline-lancaster/
Start date	2017-10-01
End date	2022-10-01
Sponsor	Gustave Roussy

Associated cell lines

Project Description

Humans are endowed with a number of advanced cognitive abilities not seen in other species. So what allows the human brain to stand out from the rest in these capabilities? In general, the brains of primates, including humans, have more neurons per unit volume than other mammals. But humans are also in the fortunate position of having the largest of the primate brains, making the number of neurons in the human cerebral cortex greatly expanded. Thus, the difference seems to be a matter of quantity, not quality. My laboratory is interested in understanding how neuron number, and thus brain size, is determined in human brain development. The research proposed here is aimed at taking an evolutionary approach to this question and comparing brain development in an in vitro 3D model system, cerebral organoids. This method, which relies on selforganization from differentiating pluripotent stem cells, recapitulates remarkably well the endogenous developmental program of the human brain. Having previously established the brain organoid approach, and more recently improved upon it with the application of bioengineering, my laboratory is in a unique position to carry out functional studies of human brain development. I propose to use this approach to compare developing human brain tissue to that of other hominid species and tease apart unique features of human neural stem cells and progenitors that allow them to generate more neurons and therefore a greater cerebral cortical size. Furthermore, we will perform transcriptomic and functional screening to identify factors underlying this expansion, followed by careful genetic substitution to test the contributions of putative evolutionary changes. In this way, we will functionally test putative human evolutionary changes in a manner not previously possible.