Target type: biologicalprocess
The process in which a region of the lung epithelium initiates an outgrowth. [GOC:dph, GOC:mtg_lung]
Lung branching morphogenesis is a complex process involving coordinated cell proliferation, differentiation, and migration, resulting in the formation of the intricate network of airways that characterize the mature lung. This process begins with the emergence of a single bud from the ventral wall of the foregut, the primordial lung. This bud then undergoes a series of iterative branching events, giving rise to the primary, secondary, and tertiary bronchi, and eventually, the bronchioles and alveoli.
The growth and branching of the lung bud are driven by interactions between epithelial and mesenchymal cells. Epithelial cells, which line the airways, play a central role in branching morphogenesis. They proliferate and differentiate to form the different cell types that make up the airways, including ciliated cells, goblet cells, and club cells. Mesenchymal cells, which surround the epithelial bud, provide structural support and produce signaling molecules that regulate epithelial cell behavior.
The process of branching involves a series of well-defined steps:
1. **Bud formation:** The initial bud emerges from the foregut epithelium and begins to grow outward. This process is driven by the activation of specific genes and signaling pathways, including the fibroblast growth factor (FGF) and Wnt pathways.
2. **Bud elongation:** The bud elongates as epithelial cells proliferate and migrate towards the distal tip of the bud. The elongation process is also regulated by signaling pathways, such as the Hedgehog pathway.
3. **Branching point formation:** At the tip of the elongating bud, a group of epithelial cells forms a "tip cell" cluster. These tip cells express specific genes and receptors that enable them to sense and respond to signals from the surrounding mesenchyme. As the bud elongates, the tip cell cluster divides and migrates, creating a new branch point.
4. **Branch formation:** Once a branch point is formed, new epithelial cells migrate from the tip cell cluster to form a new branch. The new branch then undergoes the same steps of elongation, tip cell formation, and branching, leading to the formation of a complex airway network.
The process of branching is influenced by a variety of factors, including genetic factors, environmental factors, and mechanical forces. The formation of the lung bud is influenced by the expression of specific genes, such as the transcription factor Nkx2-1. Environmental factors, such as oxygen tension and exposure to pollutants, can also affect branching morphogenesis. Mechanical forces, such as the expansion of the chest cavity during breathing, also play a role in shaping the developing lung.
Lung branching morphogenesis is a tightly regulated process that is essential for normal lung development. Disruptions in this process can lead to a variety of lung diseases, including congenital lung malformations and chronic obstructive pulmonary disease (COPD). Understanding the molecular mechanisms underlying branching morphogenesis is crucial for developing novel therapies for these diseases.'
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Protein | Definition | Taxonomy |
---|---|---|
Sonic hedgehog protein | A sonic hedgehog protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15465] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
jervine | jervine: teratogen from Veratrum grandiflorum; RN given refers to parent cpd(3beta,23beta)-isomer; structure | piperidines | |
cyclopamine | piperidines | glioma-associated oncogene inhibitor | |
cur 61414 | CUR 61414: inhibits the hedehog signaling pathway; structure in first source | ||
gdc 0449 | HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity | benzamides; monochlorobenzenes; pyridines; sulfone | antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist; teratogenic agent |
robotnikinin | robotnikinin: binds sonic hedgehog protein to block its signaling pathway; structure in first source |