Hybrid Colloquium: The early life of an extraocular motor neuron: from birth to disease to function

Abstract 

Normal vision relies on exquisite control of the eye movements. Vertebrate extraocular motor neurons control the six muscles that move each eye. We know comparatively little about the development of extraocular motor neurons and the emergence of the behaviors they subserve. This gap constrains our ability to address developmental disorders of the oculomotor system. To make progress, we have developed the larval zebrafish as a model to study the development of the oculomotor system and the behaviors it subserves. Larval zebrafish are a small vertebrate with exceptional optical and genetic access to developing neural circuits. I’ll share highlights of our lab’s efforts to understand oculomotor development. Specifically, I’ll focus on the development of extraocular motor neurons in cranial nuclei nIII/nIV that are responsible for torsional/vertical eye movements such as those that comprise the gravito-inertial vestibulo-ocular reflex. I’ll begin with published findings establishing that an extraocular motor neuron’s “birthdate” predicts which muscle it will control and where its soma lies within nIII/nIV. Next, I’ll share unpublished progress on two fronts: First, we’re working to discover the molecular determinants responsible for proper development of extraocular motor neurons. In service of this aim, we’ve generated a mutant line that has lost phox2a expression. These fish lose extraocular motor neurons in nIII/nIV leaving only the lateral rectus motor neurons in nVI intact. The eyes deviate towards the ears, similar to human patients with CFEOM type 2, who have mutations in PHOX2A. Finally, I’ll end by showing how we use a new imaging technique (Tilt In Place Microscopy, or TIPM) to map the emergence of selectivity and sensitivity in the responses of individual extraocular motor neurons across development. https://med.nyu.edu/faculty/david-schoppik