negative regulation of branching involved in lung morphogenesis

Definition

Target type: biologicalprocess

Any process that decreases the rate, frequency, or extent of the process in which a highly ordered sequence of patterning events generates the branched structures of the lung, consisting of reiterated combinations of bud outgrowth, elongation, and dichotomous subdivision of terminal units. [GOC:dph, GOC:yaf]

Negative regulation of branching involved in lung morphogenesis is a complex and tightly regulated process that ensures the proper development of the respiratory system. It involves a delicate balance of signaling pathways and cellular interactions to control the formation of the intricate branching pattern of the airways.

During early lung development, the lung bud emerges from the foregut and undergoes a series of branching events to form the trachea, bronchi, and alveoli. This branching process is driven by a combination of factors, including:

- **Epithelial-mesenchymal interactions:** The epithelial cells lining the airways interact with the surrounding mesenchymal cells, which provide structural support and secrete signaling molecules that influence epithelial branching.
- **Growth factors:** Growth factors, such as fibroblast growth factors (FGFs) and Wnt proteins, play crucial roles in regulating the proliferation, differentiation, and branching of epithelial cells.
- **Transcription factors:** Transcription factors, such as SHH and FOXA2, control the expression of genes involved in lung development, including those involved in branching morphogenesis.

Negative regulation of branching is essential to ensure that the airways develop in a controlled and organized manner. This regulation involves the inhibition of excessive branching and the promotion of proper airway shaping. Several mechanisms contribute to negative regulation of branching, including:

- **BMP signaling:** Bone morphogenetic proteins (BMPs) are secreted factors that can inhibit branching. BMPs act through a signaling pathway that involves SMAD proteins, which repress the expression of genes involved in branching.
- **TGF-beta signaling:** Transforming growth factor beta (TGF-beta) is another signaling molecule that can negatively regulate branching. TGF-beta activates a signaling pathway that leads to the expression of genes that inhibit branching.
- **Retinoic acid signaling:** Retinoic acid, a derivative of vitamin A, can also negatively regulate branching. Retinoic acid acts through a signaling pathway that involves nuclear receptors, which modulate the expression of genes involved in branching.
- **Mechanical forces:** The physical forces generated by the growing lung bud can also influence branching. For example, mechanical tension in the airway epithelium can inhibit further branching.

Disruption of negative regulation of branching can lead to lung developmental defects, such as:

- **Hypoplasia:** Reduced lung development due to insufficient branching.
- **Aplasia:** Complete absence of lung development.
- **Bronchomalacia:** Weakness of the airway walls, leading to collapse.
- **Bronchiolitis:** Inflammation of the small airways, often associated with abnormal branching.

The intricate interplay of these factors ensures the proper development of the lung, with negative regulation of branching playing a critical role in shaping the airways and preventing defects. This process is essential for maintaining normal lung function and respiratory health.'
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Proteins (1)

Compounds (18)