Related Experiment Video

Updated: Aug 6, 2026

Preparation and Culture of Rat Lens Epithelial Explants for Studying Terminal Differentiation
15:02

Preparation and Culture of Rat Lens Epithelial Explants for Studying Terminal Differentiation

Published on: September 22, 2009

Ras signaling is essential for lens cell proliferation and lens growth during development

Leike Xie1, Paul A Overbeek, Lixing W Reneker

  • 1Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.

Developmental Biology
|August 8, 2006
PubMed

Insights

Ras signaling is crucial for ocular lens growth and cell proliferation in mice. This study reveals Ras

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Biology

Background:

  • Vertebrate ocular lens growth relies on growth factor-mediated receptor tyrosine kinases (RTKs).
  • Downstream signaling pathways of RTKs in lens development are not fully understood.
  • Ras proteins are key regulators in various cellular processes, including proliferation and survival.

Purpose of the Study:

  • To investigate the role of Ras signaling in vertebrate ocular lens development.
  • To elucidate the specific functions of Ras in lens cell proliferation, differentiation, and survival.
  • To identify downstream signaling pathways affected by Ras inhibition in the lens.

Main Methods:

  • Generation of transgenic mice expressing a dominant-negative form of Ras (dn-Ras) in the ocular lens.
  • Comparative analysis of lens size, morphology, and transparency between transgenic and wild-type mice.
  • Assessment of cell proliferation using 5-bromo-2'-deoxyuridine (BrdU) labeling.
  • Evaluation of apoptosis using TUNEL or similar assays.
  • Analysis of fiber cell differentiation by examining beta- and gamma-crystallin expression.
  • Biochemical assays to measure ERK and Akt kinase activities.

Main Results:

  • Transgenic mice with dn-Ras expression exhibited smaller lenses and severely inhibited lens growth.
  • Cell proliferation was significantly reduced in the dn-Ras lenses, as indicated by lower BrdU labeling.
  • A small increase in apoptotic cells was observed in both epithelial and fiber compartments of dn-Ras lenses.
  • Primary fiber cell differentiation showed a delay, but secondary fiber cell differentiation and crystallin expression were largely unaffected.
  • Biochemical analysis revealed reduced ERK activity, but not Akt activity, in dn-Ras transgenic lenses.

Conclusions:

  • The RTK-Ras-ERK signaling pathway is essential for ocular lens cell proliferation and plays a role in cell survival.
  • Ras signaling is not required for crystallin gene expression during fiber differentiation.
  • Some aspects of lens fiber differentiation may be regulated by RTK-dependent but Ras-independent pathways.

More Related Videos

Whole Mount Imaging to Visualize and Quantify Peripheral Lens Structure, Cell Morphology, and Organization05:45

Whole Mount Imaging to Visualize and Quantify Peripheral Lens Structure, Cell Morphology, and Organization

Published on: January 19, 2024

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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...
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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Microtubules in Signaling01:22

Microtubules in Signaling

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...