Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Holt, Christine E.
Location University of Cambridge
Primary Field Cellular and Molecular Neuroscience
Secondary Field Cellular and Developmental Biology
 Research Interests
Christine Holt is interested in how axons in the developing brain navigate to their targets, how they make topographically appropriate connections, and how they are maintained into maturity. Her laboratory has focused primarily on the axons of retinal ganglion cells in the vertebrate visual system and employs molecular and live imaging strategies. These studies revealed ~mechanisms underlying the guidance of axons out of the eye, through the optic chiasm and to topographic positions in the optic tectum. Her group discovered that axons require the rapid synthesis and degradation of proteins for guidance to extrinsic cues and that hundreds of mRNAs reside in the tips of growing axons. Translation of specific mRNAs close to sites of ~signal reception (receptor activation) enables directional steering and distinct sets of proteins are synthesized in response to different cues. These studies also revealed that the axonal translatome comprises an evolving subset of enriched genes that match distinct phases in axon wiring (elongation, pruning, and synaptogenesis) and is surprisingly complex in adult axons ~with strong links to neurodegenerative disease. Collectively their findings show that local mRNA-based mechanisms play a key role in regulating axonal responses that both establish and maintain neural circuitry.

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