Related Experiment Video
Updated: Jul 14, 2026
07:26
Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
Published on: April 1, 2022
Essential role of lysyl oxidases in notochord development
John M Gansner1, Bryce A Mendelsohn, Keith A Hultman
1Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Developmental Biology
|June 5, 2007
Summary
Copper is essential for zebrafish notochord development. Inhibiting copper-dependent enzymes or specific lysyl oxidase genes (lox) causes notochord distortion, highlighting nutrient and gene interactions in skeletal development.
Area of Science:
- Developmental Biology
- Nutritional Biochemistry
- Genetics
Background:
- Copper is crucial for cuproenzyme function, impacting tissue development.
- Lysyl oxidases (LOX) are copper-dependent enzymes vital for extracellular matrix integrity.
- Notochord development in zebrafish is sensitive to copper availability.
Purpose of the Study:
- To investigate the role of copper and lysyl oxidases in zebrafish notochord development.
- To identify specific lysyl oxidase genes involved in notochord formation.
- To elucidate the interplay between nutrient availability and gene expression in skeletal development.
Main Methods:
- Utilized beta-aminopropionitrile to inhibit copper-dependent lysyl oxidases.
- Characterized zebrafish lysyl oxidase gene sequences and expression patterns.
- Performed gene knockdown studies for loxl1 and loxl5b, and assessed notochord integrity under varying copper levels.
Main Results:
- Inhibition of lysyl oxidases mimicked copper deficiency, causing notochord distortion.
- Knockdown of loxl1 resulted in notochord distortion; loxl1 and loxl5b showed overlapping roles.
- Partial knockdown of loxl1 or loxl5b sensitized embryos to copper deficiency, causing notochord distortion.
- Combined knockdown of lysyl oxidase genes or substrate (col2a1) with reduced copper exacerbated notochord abnormalities.
Conclusions:
- Copper availability and specific lysyl oxidase gene expression (loxl1, loxl5b) are critical for zebrafish notochord structural integrity.
- A complex interplay exists between genetic factors and nutrient availability in notochord development.
- Findings offer insights into the pathogenesis of axial skeletal birth defects.
Related Concept Videos
03:14Notch 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...
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...
03:14Notch 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...
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...
01:31Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
01:23Role of Matrix Metalloproteases in Degradation of ECM
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
A...
01:12Role 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...
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...
02:33Hedgehog 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...