Retinoic Acid Organizes the Zebrafish Vagus Motor Topographic Map via Spatiotemporal Coordination of Hgf/Met Signaling.

Information flow through neural circuits often requires their organization into topographic maps in which the positions of cell bodies and synaptic targets correspond. To understand how topographic map development is controlled, we examine the mechanism underlying targeting of vagus motor axons to the pharyngeal arches in zebrafish. We reveal that retinoic acid organizes topography by specifying anterior-posterior identity in vagus motor neurons. We then show that chemoattractant signaling between Hgf and Met is required for vagus innervation of the pharyngeal arches. 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 mechanism of topographic map development in which the regulation of chemoattractant signaling in space and time guides axon targeting.

COVID-19 and Kawasaki Disease: Novel Virus and Novel Case.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, we are seeing widespread disease burden affecting patients of all ages across the globe. However, much remains to be understood as clinicians, epidemiologists, and researchers alike are working to describe and characterize the disease process while caring for patients at the frontlines. We describe the case of a 6-month-old infant admitted and diagnosed with classic Kawasaki disease, who also screened positive for COVID-19 in the setting of fever and minimal respiratory symptoms. The patient was treated per treatment guidelines, with intravenous immunoglobulin and high-dose aspirin, and subsequently defervesced with resolution of her clinical symptoms. The patient's initial echocardiogram was normal, and she was discharged within 48 hours of completion of her intravenous immunoglobulin infusion, with instruction to quarantine at home for 14 days from the date of her positive test results for COVID-19. Further study of the clinical presentation of pediatric COVID-19 and the potential association with Kawasaki disease is warranted, as are the indications for COVID-19 testing in the febrile infant.

Vagus Motor Neuron Topographic Map Determined by Parallel Mechanisms of hox5 Expression and Time of Axon Initiation.

Many networks throughout the nervous system are organized into topographic maps, where the positions of neuron cell bodies in the projecting field correspond with the positions of their axons in the target field. Previous studies of topographic map development show evidence for spatial patterning mechanisms, in which molecular determinants expressed across the projecting and target fields are matched directly in a point-to-point mapping process. Here, we describe a novel temporal mechanism of topographic map formation that depends on spatially regulated differences in the timing of axon outgrowth and functions in parallel with spatial point-to-point mapping mechanisms. We focus on the vagus motor neurons, which are topographically arranged in both mammals and fish. We show that cell position along the anterior-posterior axis of hindbrain rhombomere 8 determines expression of hox5 genes, which are expressed in posterior, but not anterior, vagus motor neurons. Using live imaging and transplantation in zebrafish embryos, we additionally reveal that axon initiation is delayed in posterior vagus motor neurons independent of neuron birth time. We show that hox5 expression directs topographic mapping without affecting time of axon outgrowth and that time of axon outgrowth directs topographic mapping without affecting hox5 expression. The vagus motor neuron topographic map is therefore determined by two mechanisms that act in parallel: a hox5-dependent spatial mechanism akin to classic mechanisms of topographic map formation and a novel axon outgrowth-dependent temporal mechanism in which time of axon formation is spatially regulated to direct axon targeting.