Biology subjects

Brozost, E. M.

Publications and source records attributed to Brozost, E. M..

2 recordsLinked to original sources

bioRxiv2025

A sustained Hox program delineates brainstem neurons essential for breathing

Respiratory neurons in the brainstem must diversify and acquire unique properties during development to enable breathing at birth. Dbx1-expressing progenitors give rise to functionally and molecularly distinct excitatory respiratory populations, including rhythm-generating pre-Botzinger complex (preBotC) neurons and phrenic motor neuron (MN)-projecting rostral Ventral Respiratory Group (rVRG) neurons. These neurons are organized rostrocaudally within the ventral respiratory column (VRC) but, despite their critical functions in breathing, the mechanisms that control their organization and diversification are not well understood. Here, we generate a novel genetic tool to label brainstem neurons within the VRC. We find that rVRG neurons selectively express Hox5 genes through postnatal stages. Selective deletion of all Hox5 paralogs from Dbx1-derived neurons leads to respiratory dysfunction, perinatal death, and changes in the pattern and amplitude of phrenic MN firing. We show that Hox5 inactivation leads to a caudal expansion of putative preBotC neurons, likely at the expense of the rVRG. Collectively, our findings indicate that Hox5 proteins are required for the delineation and functional specialization of excitatory brainstem neurons essential for breathing.

neuroscience↗

bioRxiv2022

Coordinated cadherin functions sculpt respiratory motor circuit connectivity

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.

neuroscience↗