lung induction

Definition

Target type: biologicalprocess

The close range interaction of two or more cells or tissues that causes the cells of the foregut to change their fates and specify the development of the lung. [GOC:dph]

Lung induction is a complex and precisely orchestrated developmental process that transforms undifferentiated mesoderm into specialized lung tissue. This process involves a complex interplay of signaling pathways, transcription factors, and epigenetic modifications. Here's a detailed description:

1. **Specification of Lung Progenitors:**
- The first step involves the specification of lung progenitors from the lateral plate mesoderm. This occurs in response to signals from the surrounding tissues, including the foregut endoderm, the notochord, and the surrounding mesoderm.
- Key signaling pathways involved include:
- **Fibroblast Growth Factor (FGF) signaling:** FGFs, particularly FGF10, act as inductive signals from the foregut endoderm, promoting the expression of key transcription factors in the mesoderm, such as Nkx2.1.
- **Wnt signaling:** Wnt proteins, secreted from the notochord and surrounding mesoderm, contribute to the establishment of dorsal-ventral patterning within the lung field.
- **Bone Morphogenetic Protein (BMP) signaling:** BMPs from the surrounding mesoderm influence the formation of the trachea and regulate the development of the lung epithelium.

2. **Formation of the Lung Bud:**
- Once lung progenitors are specified, they begin to proliferate and form the lung bud, an initial outgrowth from the foregut endoderm.
- The lung bud is characterized by a central lumen lined by epithelial cells and surrounded by mesenchymal cells.
- Key transcription factors involved in this process include:
- **Nkx2.1:** A master regulator of lung development, promoting the expression of genes involved in epithelial cell differentiation and lung morphogenesis.
- **Sox2:** A transcription factor that regulates the maintenance of the lung epithelium.
- **Shh (Sonic hedgehog):** This signaling molecule, expressed in the ventral foregut, plays a role in lung bud formation and the development of the trachea.

3. **Branching Morphogenesis:**
- The lung bud undergoes a series of branching events, generating a complex network of airways. This process is driven by reciprocal interactions between the epithelial cells and mesenchymal cells.
- **Epithelial-Mesenchymal Interactions:**
- The epithelium produces signaling molecules, such as FGF10, that stimulate the mesenchymal cells to produce extracellular matrix (ECM) components and growth factors.
- The mesenchymal cells, in turn, respond by producing signaling molecules, such as BMP4, that influence the branching pattern of the epithelium.
- **Cell Adhesion and Migration:**
- Cell-cell interactions and cell-ECM interactions are crucial for proper branching.
- Specific adhesion molecules, such as integrins, play a role in coordinating epithelial cell movement and branching.

4. **Differentiation of Lung Cells:**
- As the lung develops, the epithelial cells differentiate into various cell types, including:
- **Type I pneumocytes:** Responsible for gas exchange.
- **Type II pneumocytes:** Produce surfactant, a substance that reduces surface tension in the alveoli, facilitating gas exchange.
- **Clara cells:** Secrete proteins that protect the airways.
- **Mesenchymal cells** differentiate into various cell types, such as smooth muscle cells, fibroblasts, and vascular cells, providing support and structure to the lung.

5. **Maturation of the Lung:**
- The final stage of lung development involves the maturation of the alveoli, the tiny air sacs where gas exchange occurs.
- This process involves a complex interplay of factors, including:
- **Vascularization:** The development of a rich network of blood vessels in the lung is essential for gas exchange.
- **Formation of the Air-Blood Barrier:** The thin barrier separating the air in the alveoli from the blood in the capillaries allows efficient gas exchange.
- **Surfactant Production:** Type II pneumocytes increase their production of surfactant, which is essential for maintaining the proper inflation of the alveoli.

6. **Postnatal Lung Development:**
- The lung continues to develop after birth, with the alveoli increasing in number and complexity.
- This process is influenced by factors such as mechanical stretch from breathing and exposure to oxygen.

Lung induction is a delicate process that requires precise coordination of many signaling pathways, transcription factors, and cellular interactions. Any disruption to this process can lead to developmental lung disorders.'
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