One of the most striking features of neurons are their highly diverse dendritic arbors. Neurons can form beautifully complex dendritic arbors allowing different neuron types to have distinct connectivity patterns and functions. Understanding how this large diversity of neuron morphology arises seems like a daunting task. Specific transcription factors have been shown to play prominent roles in generating the massive amount of neuronal diversification observed in the brain. Most of the regulators, however, have been studied separately. How the interactions of these different transcriptional regulators results in neural diversity remains to be understood.

Dr. Wesley Grueber from Columbia University is interested in studying the underlying genetic regulation of neuronal dendritic morphology. Using Drosophila as a model organism, Dr. Grueber’s lab studies how transcriptional regulators can diversify neuronal dendritic arbors. In a recent paper, “Dendritic diversification through transcription factor-mediated suppression of alternative morphologies” Dr. Grueber explores transcriptional strategies for diversifying functionally and morphologically distinct somatosensory neurons in Drosophila.

Drosophila sensory neurons are generally categorized into 4 subtypes based on their dendrite branching patterns and axon targeting. Class I sensory neurons function as proprioceptors, and Class II and III function as touch and gentle touch sensors respectively. Class IV neurons function as multimodal nociceptors. Transcriptional regulators such as Cut have been implicated in promoting the large, complex branching patterns observed in Class II-IV neurons, but is not expressed at detectable levels in neurons with less complex patterns such as Class I neurons. Performing loss-of-function and gain-of-function experiments, Grueber’s lab was able to show that the diversity of the dendritic arbor morphologies emerged from a repressive strategy involving transcription factors Cut, Pmd 1/2, Scalloped, and Vestigial (see fig. 8).

Grueber1

The findings presented in Dr. Grueber’s paper show that repressive transcriptional regulator interactions can generate dendritic diversity. By repressing other transcription factors and target genes, transcription factors can suppress alternative differentiation programs and promote diversity. The authors speculate that transcription factor-mediated suppression of “default programs” in a subset of neurons could be a mechanism by which the diversity of sensory cells types evolved, while maintaining existing modalities.

To hear more about Dr. Wesley Grueber’s research, please attend his talk on Tuesday, April 11, 2017 at 4pm in the CNCB Marilyn G. Farquhar Seminar Room.

Oscar Gonzalez is a first-year graduate student in the neurosciences graduate program and a member of Dr. Maxim Bazhenov’s lab. He is interested in the mechanisms leading to hypersynchronous activity in the brain, and the origin of resting state infra-slow fluctuations.

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