The Fishell laboratory is focused on how cellular diversity is created. Understanding how this is accomplished during development remains one of the most daunting problems in biology. In particular, Fishell’s team seeks to understand not only how the vast variety of inhibitory interneuron subtypes are generated but how they subsequently integrate into the bewildering array of neural circuits that are embedded in different brain structures.
Their working hypothesis is that this is achieved through a two-step process. The first involves genetic programs that in accordance with their birthdate create a finite number of cardinal interneuron subtypes. Following the tiling of these newly born cardinal subtypes across different brain structures, local cues act to create the definitive subtypes characteristic of the distinct cortical and subcortical areas.
Importantly, recent advances have made it clear that perturbation of this process can result in a variety of brain dysfunctions including autism spectrum disorder, intellectual disability and schizophrenia. A new and growing interest in the laboratory is therefore aimed at seeing if better understanding of these developmental events can lead to the development of new treatments for these disorders.