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Drosophila sensory neurons tile the larval body wall, Dr. Chun Han


CVRI, Room 452M Box 2240
(415) 514-2240

Daniele Canzio

Transcriptional and post-transcriptional mechanisms generating neural cell-surface diversity

The Canzio lab studies transcriptional and post-transcriptional mechanisms involved in the generation of a cell-surface diversity code in neurons. This code enables neurites (axons and dendrites) of individual neurons to distinguish between themselves and neurites from other neurons. This step is central to the ability of different neurons to connect together during brain development. A crucial aspect behind the generation of such cell-surface diversity code is the stochastic and combinatorial expression of only a small subset of clustered Protocadherins genes, randomly chosen from a total of 60. This is a remarkable task especially given that these 60 nearly-identical genes are sequestered within a chromatin state, doubly locked by DNA and H3K9 methylation and thus generally refractive to transcription. Thus, two fundamental questions remained unanswered:

(1)  How is random choice of a small number of nearly identical genes achieved?

(2)  How does localized expression occur in a repressive environment?

We use genomic, genetics, biochemical and biophysical approaches to interrogate how the exquisite coupling between 3D chromosome architecture, the underlying chromatin structure, transcription and RNA processing enables the generation of such enormous diversity of molecular barcodes in neurons.