Comparison of the 3-D patterns of the parasympathetic nervous system in the lung at late developmental stages between mouse and chicken

Abstract

Although the basic schema of the body plan is similar among different species of amniotes (mammals, birds, and reptiles), the lung is an exception. Here, anatomy and physiology are considerably different, particularly between mammals and birds. In mammals, inhaled and exhaled airs mix in the airways, whereas in birds the inspired air flows unidirectionally without mixing with the expired air. This bird-specific respiration system is enabled by the complex tubular structures called parabronchi where gas exchange takes place, and also by the bellow-like air sacs appended to the main part of the lung. That the lung is predominantly governed by the parasympathetic nervous system has been shown mostly by physiological studies in mammals. However, how the parasympathetic nervous system in the lung is established during late development has largely been unexplored both in mammals and birds. In this study, by combining immunocytochemistry, the tissue-clearing CUBIC method, and ink-injection to airways, we have visualized the 3-D distribution patterns of parasympathetic nerves and ganglia in the lung at late developmental stages of mice and chickens. These patterns were further compared between these species, and three prominent similarities emerged: (1) parasympathetic postganglionic fibers and ganglia are widely distributed in the lung covering the proximal and distal portions, (2) the gas exchange units, alveoli in mice and parabronchi in chickens, are devoid of parasympathetic nerves, (3) parasympathetic nerves are in close association with smooth muscle cells, particularly at the base of the gas exchange units. These observations suggest that despite gross differences in anatomy, the basic mechanisms underlying parasympathetic control of smooth muscles and gas exchange might be conserved between mammals and birds.

Cellular Distribution and Intracellular Localization of Different Sizes of Fluorescent Thiol-Organosilica Particles in Mouse Lungs

“…These distribution patterns were consistent with previously reported lung surface images obtained in the administration experiments using fluorescent ink of a highlighter pen. 23 However, the fluorescent ink experiment showed more homogeneous fluorescence in the fluorescent area, and the lung surface showed a patchier pattern comprising a slightly high or low fluorescence intensity area. These findings are in agreement with those of a previous study on fluorescent particles.…”

Lung patterning: Is a distal‐to‐proximal gradient of cell allocation and fate decision a general paradigm?

“…Single-cell analysis has defined new lung cell types or subtypes based on their transcriptomes, [36] but in vivo tracing and function of these new cell types or subtypes are underexplored. Both blood vessels [37] and the autonomic nerves [38,39] follow the trajectory of lung branches. Together, the airways/saccules, blood vessels, and nerves form an integrated functional unit.…”

Differential developmental blueprints of organ-intrinsic nervous systems

“…Many visceral organs have their own intrinsic nervous system, including the gut (enteric nervous system, ENS, ‘second brain’ on the gut 1 ), heart (the intrinsic cardiac nervous system, ICNS, ‘little brain’ on the heart 2 ), pancreas (intrapancreatic neurons 3,4 ), and lung (intrapulmonary neurons 5,6 , Extended Data Fig. 1).…”