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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Related Experiment Video

Updated: Sep 26, 2025

Studying Wnt Signaling During Patterning of Conducting Airways
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Wnt5a Promotes AT1 and Represses AT2 Lineage-Specific Gene Expression in a Cell-Context-Dependent Manner.

Changgong Li1, Neil Peinado1, Susan M Smith1

  • 1Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center, USC Keck School of Medicine and Children's Hospital Los Angeles, CA, USA.

Stem Cells (Dayton, Ohio)
|April 16, 2022
PubMed
Summary

Wnt5a signaling selectively promotes alveolar type 1 cell differentiation and represses type 2 cells, ensuring lung development balance. This finding is conserved across species.

Keywords:
AT1AT2Wnt signalingWnt5alung developmentlung epithelial progenitororganoid

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Area of Science:

  • Pulmonary Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Lung maturation involves complex differentiation of specialized alveolar cell types, including critical alveolar type 1 (AT1) cells for gas exchange.
  • AT1 cells originate from embryonic progenitors and postnatal surfactant protein C-expressing (Sftpc+) cells.
  • Wnt5a, a non-canonical Wnt ligand, was previously identified as essential for AT1 cell differentiation during lung saccular development.

Purpose of the Study:

  • To investigate the precise role of Wnt5a in AT1 cell differentiation and its impact on alveolar epithelial cell balance.
  • To characterize a novel conditional Wnt5a gain-of-function mouse model for studying lung development.

Main Methods:

  • Generation and analysis of a conditional Wnt5a gain-of-function mouse model.
  • Assessment of alveologenesis, cell proliferation, and lineage-specific gene expression (AT1 and AT2).
  • Analysis of Wnt5a effects in distinct alveolar epithelial cell subpopulations (Sftpchigh and Sftpclow) and human fetal lung cells.

Main Results:

  • Neonatal Wnt5a gain-of-function disrupted alveologenesis by inhibiting proliferation and downregulating canonical Wnt signaling.
  • Wnt5a promoted AT1 lineage gene expression while repressing AT2 lineage gene expression in Sftpclow cells.
  • In Sftpchigh cells, Wnt5a increased AT1 gene expression but did not affect AT2 genes or canonical Wnt signaling.
  • Wnt5a's selective regulatory role in AT1/AT2 balance was conserved in human fetal lung epithelial cells.

Conclusions:

  • Wnt5a acts as a selective regulator, promoting AT1 cell differentiation and inhibiting AT2 cells, thereby maintaining the proper AT1/AT2 balance crucial for lung development.
  • The findings highlight Wnt5a's complex, context-dependent role in lung alveolarization and its evolutionary conservation.