Related Experiment Video

Updated: Aug 18, 2026

Quantification of Orofacial Phenotypes in Xenopus
09:26

Quantification of Orofacial Phenotypes in Xenopus

Published on: November 6, 2014

Inhibition of retinoic acid receptor-mediated signalling alters positional identity in the developing hindbrain

J van der Wees1, J G Schilthuis, C H Koster

  • 1Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.

Development (Cambridge, England)
|January 13, 1998
PubMed

Insights

Retinoic acid receptors (RARs) are crucial for early neural development. Inhibiting RAR/RXR heterodimers in Xenopus embryos disrupted hindbrain patterning, revealing RARs

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Neuroscience

Background:

  • Retinoids are vital signaling molecules regulating gene expression through nuclear receptors, RARs and RXRs.
  • These receptors form heterodimers (RAR/RXR) or homodimers (RXR/RXR), influencing various developmental processes.
  • Understanding retinoid receptor function is critical for deciphering early neural development and potential teratogenic effects.

Purpose of the Study:

  • To investigate the specific roles of retinoic acid receptors (RARs) in early neural development.
  • To determine the contribution of RAR/RXR heterodimer activity versus RXR homodimer activity in retinoid-induced teratogenesis.
  • To elucidate the involvement of RARs in hindbrain patterning during embryonic development.

Main Methods:

  • Expression of a dominant-negative RARbeta in early Xenopus embryos.
  • Assessment of transactivation mediated by RAR/RXR heterodimers and RXR homodimers.
  • Analysis of retinoid-induced teratogenesis and embryonic phenotypes, including hindbrain development and gene expression patterns (Krox-20).

Main Results:

  • Dominant-negative RARbeta specifically inhibited RAR/RXR heterodimer-mediated transactivation but not RXR homodimer activity.
  • Both all-trans-retinoic acid and 9-cis-retinoic acid-induced teratogenesis were effectively blocked by dominant-negative RARbeta, confirming the requirement for RAR/RXR activity.
  • Embryos expressing dominant-negative RARbeta exhibited hindbrain disorganization, Mauthner cell multiplication, and expanded Krox-20 expression, suggesting a transformation towards rhombomere 3-5 identity.
  • Forebrain, midbrain, and spinal cord development were comparatively less affected.

Conclusions:

  • RAR/RXR heterodimer transactivation is essential for retinoid teratogenesis.
  • RXR homodimer activation does not contribute to retinoid teratogenesis.
  • RARs play a significant role in the patterning and identity specification of the embryonic hindbrain.

More Related Videos

Quantitative Measurement of Relative Retinoic Acid Levels in E8.5 Embryos and Neurosphere Cultures Using the F9 RARE-Lacz Cell-based Reporter Assay09:49

Quantitative Measurement of Relative Retinoic Acid Levels in E8.5 Embryos and Neurosphere Cultures Using the F9 RARE-Lacz Cell-based Reporter Assay

Published on: September 6, 2016

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies09:04

Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies

Published on: April 22, 2017

Related Concept Videos

Determination01:51

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
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 Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
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...