Biology subjects

Isabella, A. J.

Publications and source records attributed to Isabella, A. J..

4 recordsLinked to original sources

bioRxiv2026

Distinct transcriptional programs define cranial motor neuron subtypes during vertebrate development

Cranial motor neurons (cMNs), form discrete nuclei that control diverse behaviors such as eye movement, feeding, facial expression, and regulation of visceral organ function. However, the developmental programs that drive cMN target choices and functional specialization have not been comprehensively studied in any vertebrate. Here, we present an integrated single-cell RNA-sequencing atlas of zebrafish cMN development and perform extensive validation by HCR in situ hybridization. We find that each cranial motor nucleus expresses a distinct transcriptional signature, and in many cases, we identify transcriptional correlates to functional subtypes within individual nuclei. We find that identity often precedes axon targeting, indicating that cranial motor neuron fate is genetically specified early in development. These distinct identities are shaped by the intersection of shared function, rhombomere origin, and developmental time. A cross-species comparison between zebrafish and mouse reveals that these genetic programs are conserved.

developmental biology↗

bioRxiv2023

Position-independent refinement of vagus motor neuron wiring

Motor neurons in the central nervous system often lie in a continuous topographic map, where neurons that innervate different body parts are spatially intermingled. This is the case for the efferent neurons of the vagus nerve, which innervate diverse muscle and organ targets in the head and viscera for brain-body communication. It remains elusive how neighboring motor neurons with different fixed peripheral axon targets develop the separate somatodendritic (input) connectivity they need to generate spatially precise body control. Here we show that vagus motor neurons in the zebrafish indeed generate spatially appropriate peripheral responses to focal sensory stimulation even when they are transplanted into ectopic positions within the topographic map, indicating that circuit refinement occurs after the establishment of coarse topography. Refinement depends on motor neuron synaptic transmission, suggesting that an experience-dependent periphery-to-brain feedback mechanism establishes specific input connectivity amongst intermingled motor populations.

neuroscience↗

bioRxiv2021

Met is required for oligodendrocyte progenitor cell migration in Danio rerio

During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.

neuroscience↗

bioRxiv2019

Retinoic acid organizes the vagus motor topographic map via spatiotemporal regulation of Hgf/Met signaling

The topographic map, in which the positions of neuron cell bodies correspond with the positions of their synaptic targets, is a major organizational motif in the nervous system. To understand how topographic axon targeting is controlled during development, we examine the mechanism underlying topographic innervation of the pharyngeal arches by the vagus motor nerve in zebrafish. We reveal that Retinoic Acid organizes the topographic map by specifying anterior-posterior identity in post-mitotic vagus motor neurons. We then show that chemoattractant signaling between hepatocyte growth factor (Hgf) and the Met receptor is required for pharyngeal arch innervation by the vagus motor nerve. Finally, we find that Retinoic Acid controls the spatiotemporal dynamics of Hgf/Met signaling to coordinate axon targeting with the developmental progression of the pharyngeal arches and show that experimentally altering the timing of Hgf/Met signaling is sufficient to redirect axon targeting and disrupt the topographic map. These findings establish a new mechanism of topographic map development in which regulation of chemoattractant signaling in both space and time guides axon targeting.

developmental biology↗