Abstract: Series 106, Lecture 4

The Harvey Lectures Series 106 (2010—2011)

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Lecture #4: Thursday, February 17, 2011 — Time and Location

Construction of Complex Brain Circuits

Alexandra Joyner, PhD

Alexandra Joyner, PhD

Courtney Steel Chair in Pediatric Cancer Research
Professor, Gerstner Sloan-Kettering and Weill Cornell Graduate Schools
Developmental Biology Department

Sloan-Kettering Institute

New York, New York

Dr Joyner's Website

The neurons responsible for each brain circuit have a specific spatial organization optimized for the functioning of individual circuits, and to allow diverse circuits to interact with precision. How neurons become organized in 3D during development is a critical unanswered question. The cerebellum, which coordinates motor control, is an excellent system for studying this question as neurons that carry out related functions project afferent axons into the cerebellum to distinct positions along the two axes. Furthermore, the distribution of afferents reflects the intrinsic organization of the cerebellum into morphological lobules and stripes of gene expression. The Engrailed homeobox transcription factors have provided a genetic entry point for studying the relationship between intrinsic patterns within the cerebellum and afferent organization. By generating a series of conditional En mutations in mice, we uncovered that En1/2 coordinately regulate cerebellum afferent circuit organization and striped gene expression, and independently regulate morphology. Construction of complex neural circuits thus involves transcription factors acting at a pivotal point to direct both path finding of afferent projections and developmental processes within the target field.