Identifying genes that shape the wiring of long-range neocortical projections during development

This is a summer student position supervised by Benita Turner-Bridger in Petr Znamenskiy's lab.

Funding

This project will be supported by the Rosa Beddington fund, which has been established to support developmental biology and related activities in memory of Dr Beddington. Rosa was an eminent developmental biologist whose career was cut short by her untimely death. The successful candidate will be asked to write a short essay (less than a page) about the summer project, and its relevance to developmental biology, at the end of the placement. The essay will be posted on the Crick intranet and submitted for publication in the British Society for Developmental Biology newsletter.

Introduction to the science

To be able to perform its many extraordinary functions, our brain must be wired properly during development. Achieving this task is no mean feat. The human brain is thought to be made up of more than 100 billion neurons, each of which must extend cytoplasmic projections called axons that navigate towards their corresponding synaptic partners in the brain - thus, building the beginnings of connectivity architecture in our nervous system. We are interested in understanding the genes important for specifying long range connectivity patterns from the primary visual cortex (V1). This region of the brain is important for integrating, processing, and relaying visual information; its long-range connections sending this processed information to other brain regions for further higher-level processing (such as for object perception).

Revealing how these long-range connections form is fundamental for understanding how the neocortex relays sensory information across the brain, as well as helping to understand the genetic basis for neurodevelopmental disorders, e.g. autism, that are linked to altered neocortical connectivity.

About the project

The particular genes expressed by a given neuron during development can play an important role in determining its wiring patterns [1]. To investigate which genes regulate the formation of specific patterns of long-range connectivity from V1, we are using a large-scale connectivity mapping approach called MAPseq [2] combined with a CRISPR/Cas9 genetic screen to see what happens to connectivity patterns when the expression of specific genes is altered. The project will involve cutting-edge techniques to investigate the relationship between gene expression and long-range projection patterns of cortical neurons, such as CRISPR/Cas9-mediated genetic manipulations, preparation of next-generation sequencing libraries, and in situ sequencing.

About you

This project would suit a student studying biological/biomedical sciences and interested in neuroscience and developmental biology.

References

1.         Greig, L.C., Woodworth, M.B., Galazo, M.J., Padmanabhan, H. and Macklis, J.D. (2013)

            Molecular logic of neocortical projection neuron specification, development and diversity.

            Nature Reviews Neuroscience 14: 755-769. PubMed abstract

2.         Kebschull, J.M., Garcia da Silva, P., Reid, A.P., Peikon, I.D., Albeanu, D.F. and Zador, A.M. (2016)

            High-throughput mapping of single-neuron projections by sequencing of barcoded RNA.

            Neuron 91: 975-987. PubMed abstract