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Coordinated cadherin functions sculpt respiratory motor circuit connectivity

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Item Type:Preprint
Title:Coordinated cadherin functions sculpt respiratory motor circuit connectivity
Creators Name:Vagnozzi, A.N. and Moore, M.T. and Lin, M. and Brozost, E.M. and KC, R. and Agarwal, A. and Schwarz, L.A. and Duan, X. and Zampieri, N. and Landmesser, L.T. and Philippidou, P.
Abstract:Breathing, and the motor circuits that control it, are essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and type II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.
Keywords:Animals, Mice
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2022.08.02.502511
Date:4 August 2022
Official Publication:https://doi.org/10.1101/2022.08.02.502511
Related to:
https://edoc.mdc-berlin.de/23009/Final version

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