Illustration by Lindsey Leigh © 2017 lindseyleighart.com/

Illustration by Lindsey Leigh © 2017 lindseyleighart.com/

Gene regulatory networks in the nervous system

The tunicates are the sister group to the vertebrates, and the development of their nervous system closely mirrors our own. The larval nervous system of the tunicate Ciona has only 177 neurons, one of the smallest nervous systems in the animal kingdom, and its entire "connectome" has been recently mapped. The Ciona genome is also highly compact, with minimal gene duplications. This all around reduction offers an unprecedented opportunity to understand the gene networks responsible for specifying every type of neuron in a chordate nervous system.

We use RNAseq transcriptome profiling to assay global transcriptional dynamics in neural progenitors during Ciona development, and use CRISPR/Cas9 to knock out important transcription factors and their downstream targets to understand how these networks control neuronal specification, morphology, physiology, neurotransmitter identity, and connectivity. While our previous work has focused on the spinal cord homolog, the Motor Ganglion, we are also interested in understanding how the diverse neurons of the larval Brain are specified, organized, and connect to one another and to other parts of the central nervous system.

 

Cell behavior in neurodevelopment

The proper development of an animal relies on cells undergoing a variety of coordinated behaviors such as polarization, migration, and cell shape changes. Each of these in turn can be broken down into more specific subcellular processes that are performed by specific proteins acting in conserved interaction networks. Genetic deficiencies specifically affecting these cell behaviors are known to underlie certain congenital malformations and neurological disease.

We aim to pursue a systems-level understanding of cell behavior during neural development in tunicates, the invertebrates most closely related to humans. We are particularly interested in a group of only four neurons, the Bipolar Tail Neurons (BTNs), which connect touch receptors in the skin to the spinal cord. We have shown that these neurons are born from progenitors that delaminate from the neural plate borders and migrate along the mesoderm before undergoing a dramatic polarity inversion that gives them their name. We are currently investigating the regulation of the stereotyped cell behaviors observed in the BTNs.

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