Natural variation in synaptic neurotransmission of the lateral line in the blind Mexican cavefish - Project Summary Our goal is to understand the mechanisms underlying sensory system compensations during embryonic development. To address this, we turn to the Mexican tetra, Astyanax mexicanus, a fish species comprised of surface fish with eyes, and blind cavefish with non-visual sensory system compensations. The mechanosensory hair cell-containing lateral line is one of these compensating systems. Cavefish have an expanded lateral line that compensated for embryonic eye degeneration, but the developmental mechanisms underlying this are unclear. Further, the cavefish lateral line lost the function of its efferent inhibition, potentially explaining enhancements in hair cell neurotransmission compared to surface fish. Our central hypothesis is that eye degeneration directly contributes to expansion of the lateral line in blind cavefish, through changes in synaptic inhibition of hair cells during embryonic development. We designed 2 aims to directly test this hypothesis. In aim 1, we will compare the development of the lateral line between larval populations of A. mexicanus through immunohistochemistry to identify the embryonic origin of supernumerary neuromasts in blind cavefish. Using confocal imaging, we will quantify cellular components of the developing lateral line, including synaptic elements of hair cells in larval surface fish and cavefish. In aim 2, we will determine if expansions of the lateral line share developmental underpinnings with eye degeneration. We propose lens-ablations in surface fish embryos to examine the effects on lateral line development. Next, we will perform lens- transplantations between surface fish and cavefish embryos prior to eye degeneration in cavefish, to examine if lateral line phenotypes are swapped between populations. Finally, we will perform trait correlations between lateral line and eye phenotypes in larval surface fish-cavefish F2 hybrids to find if development of both sensory systems share genetic underpinnings. We expect that lateral line phenotypes are associated to eye development, meaning eye degeneration precedes and contributes to lateral line expansions in cavefish, putatively through synaptic changes, and that these traits are governed by the same set of genes. Towards completion of this project, I will receive mentorship from Dr. Johanna Kowalko, a leading scientist that applied functional genetics to study eye regression in cavefish, and Dr. Katie Kindt, a pioneer in the field of hair cell synaptic development in zebrafish. In alignment with the goals of the R16, I will actively involve 2 graduate students and a team of undergraduates that will directly contribute to all experiments towards completion of this project in the University of Puerto Rico, Medical Sciences Campus.