Key Mechanisms of Early Lung Development

生物 Wnt信号通路 细胞生物学 形态发生 成纤维细胞生长因子 刺猬信号通路 FGF10型 刺猬 转录因子 维甲酸 纤毛 信号转导 医学 遗传学 基因 受体 内科学
作者
Jun Kimura,Gail Deutsch
出处
期刊:Pediatric and Developmental Pathology [SAGE]
卷期号:10 (5): 335-347 被引量:74
标识
DOI:10.2350/07-06-0290.1
摘要

Lung morphogenesis requires the integration of multiple regulatory factors, which results in a functional air-blood interface required for gas exchange at birth. The respiratory tract is composed of endodermally derived epithelium surrounded by cells of mesodermal origin. Inductive signaling between these 2 tissue compartments plays a critical role in formation and differentiation of the lung, which is mediated by evolutionarily conserved signaling families used reiteratively during lung formation, including the fibroblast growth factor, hedgehog, retinoic acid, bone morphogenetic protein, and Wnt signaling pathways. Cells coordinate their response to these signaling proteins largely through transcription factors, which determine respiratory cell fate and pattern formation via the activation and repression of downstream target genes. Gain- and loss-of-function studies in null mutant and transgenic mice models have greatly facilitated the identification and hierarchical classification of these molecular programs. In this review, we highlight select molecular events that drive key phases of pulmonary development, including specification of a lung cell fate, primary lung bud formation, tracheoesophageal septation, branching morphogenesis, and proximal-distal epithelial patterning. Understanding the genetic pathways that regulate respiratory tract development is essential to provide insight into the pathogenesis of congenital anomalies and to develop innovative strategies to treat inherited and acquired lung disease.
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