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Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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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.
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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.
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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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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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A hair follicle or HF is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe a bulge in the human hair follicle's outer root sheath (ORS). The bulge is present between the sebaceous gland and the arrector pili muscle and is the niche for hair follicle stem cells (HFSCs). The bulge is also a niche for melanocyte stem cells, and their loss results in graying of hair. The HFSCs express Sox9 and Lhx2, which help them maintain stemness and prevent...
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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
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Dystroglycan Suppresses Notch to Regulate Stem Cell Niche Structure and Function in the Developing Postnatal

Freyja K McClenahan1, Himanshu Sharma1, Xiwei Shan1

  • 1Department of Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA.

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The extracellular matrix receptor dystroglycan is crucial for developing the brain's neural stem cell niche. It guides cell differentiation and structure formation in the postnatal subventricular zone.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • The extracellular matrix (ECM) regulates adult neural stem cell (NSC) quiescence.
  • The role of ECM in the developing subventricular zone (SVZ) niche is largely unknown.

Purpose of the Study:

  • To investigate the function of ECM and its receptor dystroglycan in the developing SVZ niche.
  • To elucidate the mechanisms by which dystroglycan influences NSC behavior and niche assembly.

Main Methods:

  • Analysis of dystroglycan function in the early postnatal SVZ.
  • Investigating the impact of dystroglycan on ependymal cell differentiation and niche structure.
  • Assessing Notch signaling pathway activation in radial glial cells.
  • Evaluating the role of dystroglycan in radial glial cell proliferation and gliogenic progenitor transition.

Main Results:

  • Dystroglycan orchestrates ECM restructuring in the developing SVZ.
  • Dystroglycan is essential for ependymal cell differentiation and niche pinwheel structure assembly.
  • Dystroglycan suppresses Notch activation, promoting multicilia gene expression (MCI, Myb, FoxJ1).
  • Loss of dystroglycan function increases oligodendrogenesis due to altered radial glial cell proliferation.

Conclusions:

  • Dystroglycan plays a critical role in assembling and regulating the SVZ neural stem cell niche during development.
  • Dystroglycan influences cell fate decisions, promoting multiciliated cell differentiation and regulating gliogenesis.