Related Experiment Video

Updated: May 20, 2026

Studying Wnt Signaling During Patterning of Conducting Airways
13:00

Studying Wnt Signaling During Patterning of Conducting Airways

Published on: October 16, 2016

Foxm1 mediates cross talk between Kras/mitogen-activated protein kinase and canonical Wnt pathways during development

I-Ching Wang1, Jonathan Snyder, Yufang Zhang

  • 1Divisions of Pulmonary Biology, Perinatal Institute of the Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH, USA. I-Ching.Wang@cchmc.org

Molecular and Cellular Biology
|July 25, 2012
PubMed

Insights

The transcription factor Foxm1 integrates Kras and Wnt/β-catenin signaling during lung development. Foxm1 deletion prevents lung abnormalities caused by activated Kras signaling.

Area of Science:

  • Developmental biology
  • Molecular signaling pathways
  • Respiratory system development

Background:

  • Kras/mitogen-activated protein kinase (MAPK) and Wnt/β-catenin pathways are crucial for lung morphogenesis.
  • The integration mechanisms of these pathways during lung development remain unclear.

Purpose of the Study:

  • To investigate the role of Foxm1 transcription factor in integrating Kras and Wnt/β-catenin signaling during lung development.
  • To elucidate the downstream targets and regulatory mechanisms of Kras signaling in the developing lung.

Main Methods:

  • Utilized mouse models with targeted deletion of Foxm1 in respiratory epithelial cells.
  • Employed Kras(G12D) activation to induce lung abnormalities.
  • Performed in vitro experiments using short interfering RNA (siRNA) to deplete Foxm1.
  • Analyzed T-cell factor (TCF) transcriptional activity and β-catenin localization.
  • Quantified Axin2 mRNA and protein levels.
  • Investigated Foxm1 binding to the Axin2 promoter region.

Main Results:

  • Foxm1 is a key downstream target of activated Kras(G12D).
  • Foxm1 deletion in respiratory epithelial cells prevented Kras(G12D)-induced lung structural abnormalities.
  • Kras/Foxm1 signaling inhibited canonical Wnt signaling in the developing lung.
  • Foxm1 decreased TCF transcriptional activity induced by activated β-catenin.
  • Foxm1 depletion led to increased nuclear β-catenin and target gene expression, with decreased Axin2 levels.
  • Foxm1 directly bound to and activated the Axin2 promoter.

Conclusions:

  • Foxm1 is essential for Kras signaling in distal lung epithelium.
  • Foxm1 integrates Kras and canonical Wnt/β-catenin signaling pathways during lung development.
  • This study provides a novel mechanism for crosstalk between these critical developmental pathways.

More Related Videos

Modeling Paracrine Noncanonical Wnt Signaling In Vitro11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

The Soft Agar Colony Formation Assay08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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 results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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 results in tumor...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...