@article {70148, title = {Emergence of Functional Heart-Brain Circuits in a Vertebrate.}, journal = {eLife}, year = {2025}, month = {2025 Dec 22}, abstract = {

The early formation of sensorimotor circuits is essential for survival. While the development and function of exteroceptive circuits and their associated motor pathways are well characterized, far less is known about the circuits that convey viscerosensory inputs to the brain and transmit visceromotor commands from the central nervous system to internal organs. Technical limitations, such as the\ in utero\ development of viscerosensory and visceromotor circuits and the invasiveness of procedures required to access them, have hindered studies of their functional development in mammals. Using larval zebrafish{\textemdash}which are genetically accessible and optically transparent{\textemdash}we tracked,\ in vivo, how cardiosensory and cardiomotor neural circuits assemble and begin to function. We uncovered a staged program. First, a minimal efferent circuit suffices for heart-rate control: direct brain-to-heart vagal motor innervation is required, intracardiac neurons are not, and heart rate is governed exclusively by the motor vagus nerve. Within the hindbrain, we functionally localize a vagal premotor population that drives this early efferent control. Second, sympathetic innervation arrives and enhances the dynamics and amplitude of cardiac responses, as neurons in the most anterior sympathetic ganglia acquire the ability to drive cardiac acceleration. These neurons exhibit proportional, integral, and derivative{\textendash}like relationships to heart rate, consistent with controller motifs that shape gain and dynamics. Third, vagal sensory neurons innervate the heart. Distinct subsets increase activity when heart rate falls or rises, and across spontaneous fluctuations, responses to aversive stimuli, and optogenetically evoked cardiac perturbations, their dynamics are captured by a single canonical temporal kernel with neuron-specific phase offsets, supporting a population code for heart rate. This temporally segregated maturation isolates three experimentally tractable regimes{\textemdash}unidirectional brain-to-heart communication, dual efferent control, and closed-loop control after sensory feedback engages{\textemdash}providing a framework for mechanistic dissection of organism-wide heart{\textendash}brain circuits.

}, issn = {2692-8205}, doi = {10.1101/2025.09.22.677693}, url = {https://doi.org/10.7554/eLife.109362.1}, author = {Hernandez-Nunez, L and Avrami, J and Shi, S and Markarian, A and Ruetten, Virginia M.S. and Boulanger-Weill, J and Zarghani-Shiraz, A and Ahrens, M and Engert, F and Fishman, M C} } @article {69773, title = {Live imaging of the extracellular matrix with a glycan-binding fluorophore.}, journal = {Nat Methods}, year = {2025}, month = {2025 Feb 06}, abstract = {

All multicellular systems produce and dynamically regulate extracellular matrices (ECMs) that play essential roles in both biochemical and mechanical signaling. Though the spatial arrangement of these extracellular assemblies is critical to their biological functions, visualization of ECM structure is challenging, in part because the biomolecules that compose the ECM are difficult to fluorescently label individually and collectively. Here, we present a cell-impermeable small-molecule fluorophore, termed Rhobo6, that turns on and red shifts upon reversible binding to glycans. Given that most ECM components are densely glycosylated, the dye enables wash-free visualization of ECM, in systems ranging from in vitro substrates to in vivo mouse mammary tumors. Relative to existing techniques, Rhobo6 provides a broad substrate profile, superior tissue penetration, non-perturbative labeling, and negligible photobleaching. This work establishes a straightforward method for imaging the distribution of ECM in live tissues and organisms, lowering barriers for investigation of extracellular biology.

}, issn = {1548-7105}, doi = {10.1038/s41592-024-02590-2}, url = {https://doi.org/10.1038/s41592-024-02590-2}, author = {Fiore, Antonio and Yu, Guoqiang and Northey, Jason J and Patel, Ronak and Ravenscroft, Thomas A. and Ikegami, Richard and Kolkman, W and Pratik Kumar and Dilan, Tanya L and Ruetten, Virginia M.S. and Ahrens, Misha B and Shroff, Hari and Wang, Shaohe and Weaver, Valarie M and Pedram, Kayvon} } @article {69440, title = {Imaging the extracellular matrix in live tissues and organisms with a glycan-binding fluorophore}, journal = {bioRxiv}, year = {2024}, month = {2024 May 10}, abstract = {

All multicellular systems produce and dynamically regulate extracellular matrices (ECM) that play important roles in both biochemical and mechanical signaling. Though the spatial arrangement of these extracellular assemblies is critical to their biological functions, visualization of ECM structure is challenging, in part because the biomolecules that compose the ECM are difficult to fluorescently label individually and collectively. Here, we present a cell-impermeable small molecule fluorophore, termed Rhobo6, that turns on and red shifts upon reversible binding to glycans. Given that most ECM components are densely glycosylated, the dye enables wash-free visualization of ECM, in systems ranging from in vitro substrates to in vivo mouse mammary tumors. Relative to existing techniques, Rhobo6 provides a broad substrate profile, superior tissue penetration, nonperturbative labeling, and negligible photobleaching. This work establishes a straightforward method for imaging the distribution of ECM in live tissues and organisms, lowering barriers for investigation of extracellular biology.

}, doi = {10.1101/2024.05.09.593460}, url = {https://www.biorxiv.org/content/early/2024/05/10/2024.05.09.593460}, author = {Fiore, Antonio and Yu, Guoqiang and Northey, Jason J. and Patel, Ronak and Ravenscroft, Thomas A. and Ikegami, Richard and Kolkman, Wiert and Kumar, Pratik and Grimm, Jonathan B. and Dilan, Tanya L. and Ruetten, Virginia M.S. and Ahrens, Misha B. and Shroff, Hari and Lavis, Luke D. and Wang, Shaohe and Weaver, Valerie M. and Pedram, Kayvon} }