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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

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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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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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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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Related Experiment Video

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Studying Wnt Signaling During Patterning of Conducting Airways
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Hox5 Genes Regulate the Wnt2/2b-Bmp4-Signaling Axis during Lung Development.

Steven M Hrycaj1, Briana R Dye2, Nicholas C Baker1

  • 1Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-2200, USA.

Cell Reports
|August 4, 2015
PubMed
Summary
This summary is machine-generated.

Hox5 genes are crucial for lung development, controlling mesodermal-epithelial signaling. Their absence causes severe lung defects by disrupting the Wnt2/2b-Bmp4 pathway.

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Area of Science:

  • Developmental biology
  • Genetics
  • Molecular biology

Background:

  • Hox genes are essential for embryonic development and organogenesis.
  • Proper lung development relies on intricate signaling between mesenchyme and epithelium.
  • The specific roles of Hox5 paralogs in lung development remain largely uncharacterized.

Purpose of the Study:

  • To investigate the redundant roles of the three Hox5 paralogous genes in lung development.
  • To elucidate the molecular mechanisms by which Hox5 genes regulate lung patterning.
  • To identify the signaling pathways influenced by Hox5 genes during lung organogenesis.

Main Methods:

  • Generation and analysis of Hoxa5;Hoxb5;Hoxc5 triple-mutant mouse embryos.
  • Analysis of gene expression patterns in lung mesenchyme and epithelium.
  • In vitro rescue experiments using Wnt2/2b-enriched media on lung explants.

Main Results:

  • Triple mutation of Hoxa5, Hoxb5, and Hoxc5 results in severely hypoplastic lungs with impaired branching and patterning.
  • Hox5 genes, expressed in the lung mesoderm, regulate signaling to both mesenchyme and epithelium.
  • Loss of Hox5 function leads to decreased Wnt2/2b expression and downstream Wnt2/2b targets (Lef1, Axin2, Bmp4) in the lung mesenchyme.
  • Wnt2/2b signaling can rescue lung patterning defects and restore Bmp4 expression in Hox5-deficient lungs.

Conclusions:

  • Hox5 genes play essential, redundant roles in lung development.
  • Hox5 genes act as upstream regulators in the mesoderm, controlling the Wnt2/2b-Bmp4 signaling axis.
  • This signaling axis is critical for proper lung mesenchyme-epithelium crosstalk and overall lung patterning.