Language

English

Publication Date

4-15-2025

Journal

Development

DOI

10.1242/dev.204346

PMID

40177910

PMCID

PMC12070062

PubMedCentral® Posted Date

4-28-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Unidirectional airflow in the avian lung enables gas exchange during both inhalation and exhalation. The underlying developmental process and how it deviates from that of the bidirectional mammalian lung are poorly understood. Sampling key developmental stages with multiscale 3D imaging and single-cell transcriptomics, we delineate morphogenic, molecular and cellular features that accommodate the unidirectional airflow in the chicken lung. Primary termini of hyper-elongated branches undergo proximal-short and distal-long fusions, forming parabronchi for air conduction. Through the parabronchial smooth muscle, neoform termini extend radially to form gas-exchanging alveoli. Supporting this radial alveologenesis, branch stalks halt their proximalization, defined by SOX9-SOX2 transition, and become SOX9low parabronchi. Primary and secondary vascular plexi interface with primary and neoform termini, respectively. Single-cell and Stereo-seq spatial transcriptomics reveal a third, chicken-specific alveolar cell type expressing KRT14, hereby named luminal cells. Luminal, alveolar type 2 and alveolar type 1 cells sequentially occupy concentric zones radiating from the parabronchial lumen. Our study explores the evolutionary space of lung diversification and lays the foundation for functional analysis of species-specific genetic determinants.

Keywords

Animals, Lung, Chickens, Chick Embryo, Single-Cell Analysis, Transcriptome, Morphogenesis, Gene Expression Regulation, Developmental, Pulmonary Alveoli, Adaptation, Physiological, Chicken lung development, Comparative single-cell genomics, Spatial transcriptomics, Lung evolution, Branching morphogenesis

Published Open-Access

yes

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