S. Lodato, Humanitas University - Clinical and Research Center, IRCCS - Milan

Friday, 23th March – h. 14:30
Seminars Room, NICO

Simona Lodato, PhD
Dep. of Biomedical Sciences, Humanitas University- Humanitas Clinical and Research Center, IRCCS – Milan

Decoding neuronal diversity of the mammalian cerebral cortex in development, evolution and disease

The mammalian cerebral cortex contains an unparalleled diversity of neuronal subtypes, which is the ultimate result of complex, spatially and temporally controlled differentiation processes of defined pool of neuronal progenitors. While the distinct molecular logics and the defining principles that control the generation of such heterogeneous neuronal output have just begun to be elucidated, it is well appreciated that multiple genetic and environmental factors concur to the establishment of distinct classes of both excitatory projection neurons (PNs) and inhibitory interneurons (INs) that populate the cerebral cortex. Balanced activity indeed relies on the precise assembly of specialized neuronal circuits that involve PN and IN subtypes.
 
Although they have different developmental origins, these two classes of neurons ultimately co-reside in the cortex,  where they assemble into functional local microcircuitry. The developmental events governing the proper interaction between PNs and INs are poorly understood, in particular the cellular and molecular events that direct interneurons to position precisely within specific cortical layers. We have previously reported that the acquisition of a distinct subtype-specific PN identity uniquely and differentially determines the development of cortical microcircuit assembly.

We are currently investigating the intrinsic molecular mechanisms and activity-dependent mechanisms that control specific pairing between distinct subtypes of PNs and INs in the early stages of radial migration of cortical interneurons. To address this question, we FACS-purified and transcriptionally profiled PN and IN subtypes, over multiple developmental time points from both murine (embryonic and postnatal) and human corteces (fetal). In particular, by combining standard isolation strategies to a recently developed purification method that does not require genetic labelling of the distinct neuronal subtypes, we are building a critical resource of gene expression data from multiple subtypes of PNs and INs isolated from the murine neocortex and, in parallel, from human fetal cortex.

Using custom bioinformatic analysis we aim at identifying evolutionally conserved (as well as species specific) principles of diversity generation, while identifying candidates potentially relevant for the lamination and integration of  interneurons within the cortex. this will shed light on the molecular logics behind assembly of specialized cortical circuits, which are often targets of devastating neurodevelopmental disorders

Host: Alessandro Vercelli