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Glial cells are essential for functionality of the nervous system. Growing evidence underscores the importance of astrocytes; however, analogous astroglia in peripheral organs are poorly understood. Using confocal time-lapse imaging, fate mapping, and mutant genesis in a zebrafish model, we identify a neural crest–derived glial cell, termed nexus glia, which utilizes Meteorin signaling via Jak/Stat3 to drive differentiation and regulate heart rate and rhythm. Nexus glia are labeled with gfap , glast , and glutamine synthetase , markers that typically denote astroglia cells. Further, analysis of single-cell sequencing datasets of human and murine hearts across ages reveals astrocyte-like cells, which we confirm through a multispecies approach. We show that cardiac nexus glia at the outflow tract are critical regulators of both the sympathetic and parasympathetic system. These data establish the crucial role of glia on cardiac homeostasis and provide a description of nexus glia in the PNS.

Glial cells are essential for functionality of the nervous system. Growing evidence underscores the importance of astrocytes; however, analogous astroglia in peripheral organs are poorly understood. Using confocal time-lapse imaging, fate mapping, and mutant genesis in a zebrafish model, we identify a neural crest–derived glial cell, termed nexus glia, which utilizes Meteorin signaling via Jak/Stat3 to drive differentiation and regulate heart rate and rhythm. Nexus glia are labeled with gfap, glast, and glutamine synthetase, markers that typically denote astroglia cells. Further, analysis of single-cell sequencing datasets of human and murine hearts across ages reveals astrocyte-like cells, which we confirm through a multispecies approach. We show that cardiac nexus glia at the outflow tract are critical regulators of both the sympathetic and parasympathetic system. These data establish the crucial role of glia on cardiac homeostasis and provide a description of nexus glia in the PNS. Do astrocyte-like cells exist in the peripheral nervous system? This study reveals that astrocyte-like cells termed cardiac nexus glia populate the heart, and that these cells are important for cardiac homeostasis, modulating heart rate and rhythm during development.

The nervous system is an expansive network of neurons and glia that is essential for health. Although vast, the system can be segregated into two main parts: the central nervous system (CNS) and the peripheral nervous system (PNS). The PNS is then further divided into the somatic nervous system and the autonomic nervous system. Together, these peripheral systems control responses to external stimuli and organ function, respectively. In order to enact their control, neurons provide signaling throughout the body while glia serve in several necessary modulatory capacities. Given the extensive roles of the PNS in daily health and activities, it is thus prudent to understand the cellular and molecular regulators that guide its development. In this dissertation, we use super-resolution confocal time-lapse imaging, pharmacological manipulation, and mutant genesis in a zebrafish model to address this need twofold. First, we study the somatosensory system by elucidating the molecular mechanisms that guide sensory axon growth cone navigation and entry into the spinal cord. This work establishes a connection between molecules and actin stabilization in the growth cone to complete circuit development. Second, we investigate the autonomic nervous system and identify a novel glial population in the heart, which ultimately regulates cardiac function. Taken together, these findings expand upon our understanding of neuronal and glial development in the periphery.