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Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

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...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Gastrulation01:56

Gastrulation

Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata will form...

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Related Experiment Video

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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
07:26

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Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme.

Tae-Hee Kim1, Byeong-Moo Kim, Junhao Mao

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Development (Cambridge, England)
|July 14, 2011
PubMed
Summary

Hedgehog (Hh) signaling restrains Notch activity in the developing gut mesenchyme, preventing cell death and ensuring proper organ growth. This interaction is crucial for digestive tract development.

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Mouse Fetal Whole Intestine Culture System for Ex Vivo Manipulation of Signaling Pathways and Three-dimensional Live Imaging of Villus Development
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Mouse Fetal Whole Intestine Culture System for Ex Vivo Manipulation of Signaling Pathways and Three-dimensional Live Imaging of Villus Development
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Mouse Fetal Whole Intestine Culture System for Ex Vivo Manipulation of Signaling Pathways and Three-dimensional Live Imaging of Villus Development

Published on: September 4, 2014

Area of Science:

  • Developmental biology
  • Gastrointestinal physiology
  • Cell signaling

Background:

  • Digestive tract development involves coordinated epithelial-mesenchymal interactions.
  • Hedgehog (Hh) signaling from the epithelium is essential for mesenchymal growth and gut tube elongation.
  • Notch signaling is known to function in intestinal epithelial progenitors.

Purpose of the Study:

  • To investigate the role of Notch signaling in the embryonic gut mesenchyme.
  • To elucidate the interplay between Hh and Notch signaling in gastrointestinal development.

Main Methods:

  • Conditional knockout mice lacking the Notch effector gene RBP-Jκ (Rbpj) in the mesenchyme.
  • Analysis of Notch pathway activity in embryonic gut mesenchyme.
  • In vitro culture of fetal gut mesenchymal cells with recombinant sonic hedgehog.

Main Results:

  • Disruption of Rbpj in the mesenchyme led to fibroblast loss and shorter gut length.
  • Constitutive Notch activity caused mesenchymal cell loss and impaired organogenesis.
  • Hedgehog-deficient embryos exhibited Notch overactivity; Hh signaling counteracted Notch-induced cell death.

Conclusions:

  • Notch signaling is unexpectedly required in the gut mesenchyme for fibroblast survival and gut elongation.
  • A precise balance of Notch signaling is necessary for proper gastrointestinal organogenesis.
  • Endodermal Hh signaling restrains mesenchymal Notch activity, explaining Hh's role in mesenchymal cell survival and growth.