Sean M. Kelly
B.S. Boston College, 2008
5th Year MSTP
3rd Year Neuroscience Graduate Student
Advisor: Josh Huang, PhD
Department: Cold Spring Harbor Laboratory
Graduate Program: Neuroscience
Title: Chandelier cells and the developmental genetic basis of cortical interneuron identity
Abstract:
Sean Kelly1,2, Z. Josh Huang1,2
1 – Stony Brook MSTP, Graduate Program in Neuroscience
2 – Cold Spring Harbor Laboratory, Department of Neuroscience
The mammalian neocortex consists of a constellation of functional areas, each with a specific pattern of neuronal connections required for various aspects of perception, cognition, and volitional control of motivated behaviors. The cellular building blocks of cortical circuits include a vast assortment of different types of long projecting glutamatergic pyramidal neurons as well as local GABAergic inhibitory interneurons. GABAergic interneurons in particular are a diverse family of discrete cell types, which regulate neuronal firing activity through a vast array of morphological, molecular, synaptic, and electrophysiological properties. Most types of cortical interneurons in rodents arise from three neurogenic zones in the embryonic forebrain: the medial and caudal ganglionic eminences (MGE, CGE), and the preoptic area (POA).
To approach a complete understanding of interneuron development, our studies have focused on characterizing the entire life history of the chandelier cell, arguably the most distinct and uniform GABAergic interneuron cell type yet to be described. Chandelier cells (ChCs) have an unmistakable axon arbor of hundreds of vertically arranged cartridge synapses, each of which specifically innervates the axon initial segment of a pyramidal cell, the site where action potentials are generated. ChCs originate from Nkx2.1+ progenitors in the MGE and migrate to cortex during circuit assembly, where they are uniquely positioned to coordinate the firing of networks of pyramidal cells while receiving long-range inputs from all cortical layers and many subcortical brain regions. Using intersectional genetic fate mapping and novel birth dating techniques, we provide an experimental system to examine for the first time the cellular and molecular nature of progenitors that produce a well-defined cell type in cortex. Through these studies, we hope to discover and characterize distinct pools of Nkx2.1+ progenitors that distribute ChCs to major cerebral subdivisions and thus yield functional ChC subtypes via temporal regulation of neurogenesis in the MGE and VGZ during mid-to-late gestation.
Publications:
(MSTP-supported publications indicated with an *)
Goldstein JA, Kelly SM, LoPresti PP, Heydemann A, Earley JU, Ferguson EL, Wolf MJ, McNally EM. (2011). TGFb signaling drives progression in muscular dystrophy.Human Molecular Genetics 20; 20(5):894-904. PMID: 21138941.
Lai, L., Leone, T. C., Zechner, C., Schaeffer, P. J., Kelly, S. M., Flanagan, D. P., Medeiros, D. M., Kovacs, A., and Kelly, D. P. (2008) Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart, Genes Dev 22, 1948-1961.
