PhD Transfer Exam – Urfa Arain (Erclik lab)

PhD Transfer Exam

Thursday May 18^th, 2:30 pm – Rm. DV 3138, University of Toronto at Mississauga

Urfa Arain (Erclik lab)

“Mechanisms underlying neuronal migration in the Drosophila optic lobe“

Abstract

Our ability to see the world around us relies on the precise assembly of neurons into complex circuits in the visual centers of our brain. The Drosophila medulla, which comprises the largest structure of the optic lobe, is an excellent model to explore neural circuit assembly due to its precise organization of 40,000 neurons across 800 columns. These neurons can be subdivided into two major classes: uni-columnar and multi-columnar. Uni-columnar neurons are born throughout the entire medulla and have small dendritic arborizations that contact a single column. In contrast, multi-columnar neurons are fewer in number and have large arborizations that contact several columns. During development, the majority of multi-columnar neurons are born in a restricted region and express the transcription factor Vsx1. Subsequently, they migrate up to 60 microns from where they are born to cover the entire medulla. The goal of my research is to identify the mechanisms that underlie the migration of Vsx1-derived multi-columnar neurons during development. I have found that migration occurs as a two-step process that begins 20 hours after puparium formation (APF) and continues until 50 hours APF. Surprisingly, the cell bodies of multi-columnar neurons initially migrate with a ventral bias that persists for at least 10 hours of pupal brain development, after which they cover the entire dorsoventral axis of the medulla. Additionally, the axons of Vsx1-derived multi-columnar neurons target locally in the developing neuropil prior to migration, indicating that their movement is likely independent of axonal targeting. Remarkably, the steroid hormone Ecdysone plays a key role in the process; transgenic flies expressing a dominant-negative form of the Ecdysone receptor in Vsx1 neurons show a cluster of cell bodies that fail to migrate in the adult medulla. In this PhD, I propose to describe the development of an individual multi-columnar neuron using genetic and live-imaging techniques. I will also investigate the role played by Ecdysone in migration by generating mutant MARCM clones and following them developmentally. Lastly, I intend to explore whether heterotypic signals from adjacent cell types or homotypic signals within the same subtype affect the migration of multi-columnar neurons through attractive or repulsive cues. It is anticipated that the results of this project will inform our understanding of neuronal development, neural circuit assembly and neurodevelopmental disorders in which these processes are disrupted, such as autism.