Lateral line sensory nerve guidance by a migrating cell collective

The National Institute on Deafness and Other Communication Disorders awarded Weill Medical College of Cornell University $109,652 under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) on September 18, 2025.

The award funds research into lateral line sensory nerve guidance mechanisms using zebrafish posterior lateral line nerve as a model for understanding cochlear nerve development. Cochlear nerve deficiency is a congenital malformation that results in severe or profound hearing loss; the research aims to clarify developmental processes and identify therapeutic targets for this condition. The project investigates how the tissue environment impacts nerve development through three aims: characterizing adhesion molecules in nerve and primordium co-migration, examining how location and timing of secreted cues affect nerve extension and adhesion, and mapping gene expression progressions in nerve neurons and primordium cells to evaluate intercellular signaling composition. Work integrates in vivo imaging of fluorescently labeled growth cones with genetic and experimental manipulations in zebrafish.

Work is performed at Weill Medical College in New York, New York. The period of performance runs from September 18, 2025 through September 17, 2029. The research is conducted under the direct mentorship of Dr. A. J. Hudspeth at Rockefeller University.

Abstract

The cochlear nerve, critical for hearing, relies on precise extension and connectivity during development. Cochlear nerve deficiency (CND) is a congenital malformation resulting in an absent or small cochlear nerve that leads to severe or profound hearing loss with permanent and detrimental effects on patient quality of life. To better understand CND pathophysiology, the mechanisms guiding cochlear nerve development must be understood. This project's objective is to determine how the in vivo tissue environment impacts cochlear nerve development, using the zebrafish posterior lateral line nerve (plln) as a model. Similar to processes in the mammalian cochlea, the zebrafish plln extends alongside a migrating cell collective called the primordium. Our hypothesis is that secreted signals from the primordium contribute to the dynamics of adhesive signaling in plln development. These mechanisms will be investigated in zebrafish by integrating in vivo imaging of fluorescently labeled growth cones and primordium cells with genetic and experimental manipulations. In aim 1, the role of specific adhesion molecules in the CO-migration of the plln and primordium will be characterized. Aim 2 will examine how the location and timing of secreted cues impact plln extension and adhesion to the primordium. Lastly, aim 3 will focus on mapping the progressions in gene expression of neurons forming the plln and the cells of the primordium over time as a way to evaluate the relative composition of intercellular signaling. These studies will clarify how adhesive and secreted cues cooperate to ensure robust plln development, offering insight into the developmental process of the cochlear nerve. Findings in these areas support the search for future therapeutic targets for CND. The described studies will be carried out under the direct mentorship of DR. A. J. Hudspeth at the rockefeller university within the supportive weill cornell/rockefeller/sloan kettering TRI-institutional MD-PHD program environment. This fellowship constitutes an important career milestone for dual-degree students seeking to become independent investigators.