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Biology subjects

Alsina, B.

Publications and source records attributed to Alsina, B..

3 recordsLinked to original sources

The Cxcl14 chemokine defines pioneer axon guidance and early circuit assembly in the inner ear

The nervous system wiring requires the precise coordination of axon guidance, neuronal migration, and target cell recognition. Here, we show that inner ear circuit formation, relies on pioneer cells extending an axonal scaffold that selectively target nascent hair cells. High spatiotemporal imaging of pioneer axons reveal how they navigate through the cranial environment, establish dynamic cell-cell contacts with other axons to finally stabilize in target cells. These pioneer axons are required not only for follower axon growth but also for coordinated migration of follower neurons, revealing a cellular hierarchy underlying circuit assembly. We identify the chemokine Cxcl14 as a novel instructive guidance cue regulating pioneer axon extension, turning, and fasciculation at discrete cellular decision points. Loss of Cxcl14 disrupts axonal navigation, compromises synaptic organization in hair cells, and impairs mechanosensory-based behavior. Together, our findings establish a new chemokine-based mechanism linking pioneer axon guidance to early sensory circuit assembly necessary for building mechanosensory networks.

developmental biology↗

Role of pioneer neurons and neuroblast behaviors on otic ganglion assembly

Cranial ganglia are aggregates of sensory neurons that mediate distinct types of sensation. It is little understood how individual neurons coalesce, distribute and shape the ganglion. The statoacoustic ganglion (SAG) displays several lobes spatially arranged to properly connect with hair cells of the inner ear. To investigate the cellular behaviors involved in the 3D organization of the SAG, we use high resolution confocal imaging of single cell labeled zebrafish neuroblasts (NB), photoconversion, photoablation and genetic perturbations. We find that otic NB delaminate out of the otic epithelium in an EMT-like manner, rearranging apical polarity and primary cilia proteins. We also show that, once delaminated, NB migrate directionally and actively, requiring RhoGTPases. Interestingly, cell tracking of individual delaminated NB reveals that NB migrate and coalesce around a small population of pioneer SAG neurons. These pioneer SAG neurons are not from otic placode origin and populate the coalescence region before otic neurogenesis begins. Upon ablation of these cells, migratory pathways of delaminated NB are disrupted and, consequently, SAG shape is affected. Altogether, this work shows for the first time the role of pioneer SAG neurons in orchestrating SAG development. Summary StatementLittle is known how cranial sensory ganglia organize in 3D. We unveil the repertoire of cellular behaviours underlying statoacoustic morphogenesis and its dependence on relevant pioneer neurons.

developmental biology↗

Sensory neurogenesis depends on vascular-neuronal filopodia contacts and blood flow

In many organs, stem cell function depends on the communication with their niche partners. Cranial sensory neurons develop in close proximity to blood vessels, however whether vasculature is an integral component of their niches is yet unknown. Here, two separate, novel roles for vasculature in cranial sensory neurogenesis in zebrafish are uncovered. The first involves precise spatiotemporal endothelial-neuroblast cytoneme contacts and Dll4-Notch signalling to restrain neuroblast proliferation. Secondly, we find that blood flow onset triggers a transcriptional response to modify neuroblast metabolic status and is required for sensory neuron differentiation. In contrast, no role of sensory neurogenesis in vascular development is found, suggesting a unidirectional signalling from vasculature to sensory neuroblasts. Altogether, we demonstrate that the cranial vasculature constitutes a hitherto unrecognized niche component of the sensory ganglia that regulates the pace of their growth and differentiation dynamics.\n\nHighlights{diamondsuit} Vasculature is part of the cranial sensory ganglia niche and regulates neurogenesis.\n{diamondsuit}Cytoneme contacts between endothelial cells and sensory neuroblasts are required for neuroblast quiescence.\n{diamondsuit}Endothelial Dll4 and neuroblast Notch1 signal to regulate the growth of cranial sensory ganglia.\n{diamondsuit}Initiation of blood flow triggers a transcriptional metabolic switch and sensory neuronal differentiation.

developmental biology↗