Related Experiment Video
Updated: Aug 13, 2026
Analysis of Cell Differentiation, Morphogenesis, and Patterning During Chicken Embryogenesis Using the Soaked-Bead Assay
Published on: January 12, 2022
Transforming growth factor-beta and bone morphogenetic proteins: cooperative players in chick and murine programmed
Andreas G Franke1, Christian Gubbe, Marion Beier
1Department of Neuroanatomy, Center of Anatomy, University of Goettingen, 37075 Goettingen, Germany.
Abstract:
Transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) are extracellular molecules known to mediate programmed cell death (PCD) in the developing retina. In the present study, we investigated the expression profiles and activity levels of ligands and receptors of the TGF-beta and BMP4 family during the physiological PCD periods of the developing chick and mouse retina and possible interactions of both proapoptotic molecules in mediating apoptosis in chick and murine retinal whole-mount cultures. Immunocytochemical double-labeling studies with the established ganglion cell marker Islet revealed overlapping expression patterns for TGF-beta and BMP4 ligands and receptors on the surface of retinal ganglion cells. The biphasic peak of activity and expression levels of TGF-beta and BMP4 ligands and receptors, revealed by Western blots and mink lung epithelial cell (MLEC) assays, coincided with the two main periods of retinal chick and murine PCD. In organotypic retinal cultures, we were able to increase apoptosis over basal levels by application of recombinant TGF-beta or BMP4. Double-factor treatment induced an additional increase of apoptosis, suggesting a cooperation of both proapoptotic pathways. A significant increase in the number of apoptotic cells in the ganglion cell layer was observed in a TUNEL staining of retinal whole mounts treated with recombinant TGF-beta or BMP4, suggesting a concerted action of both factors in triggering ganglion cell death. Blockage experiments revealed that both pathways do not interact at the ligand, receptor, or Smad protein level but converge at the transcriptional level of the TGF-beta immediate-early response gene TIEG and the transcriptional coactivator Gcn5.
Insights
Transforming growth factor-beta (TGF-beta) and bone morphogenetic protein 4 (BMP4) signaling pathways cooperate to induce programmed cell death in developing retinal ganglion cells. These pathways converge transcriptionally, highlighting a key mechanism in retinal development.
Area of Science:
- Developmental biology
- Cell biology
- Neuroscience
Background:
- Transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) are extracellular signaling molecules.
- These molecules are known to mediate programmed cell death (PCD) in the developing retina.
Purpose of the Study:
- To investigate the expression profiles and activity of TGF-beta and BMP4 family ligands and receptors during retinal PCD.
- To explore the interaction of these proapoptotic molecules in chick and mouse retinal cultures.
Main Methods:
- Immunocytochemical double-labeling using the ganglion cell marker Islet.
- Western blots and mink lung epithelial cell (MLEC) assays to determine ligand and receptor activity.
- Organotypic retinal cultures treated with recombinant TGF-beta or BMP4, followed by TUNEL staining.
Main Results:
- Overlapping expression of TGF-beta and BMP4 ligands and receptors on retinal ganglion cells.
- Biphasic peaks in TGF-beta and BMP4 activity and expression coincided with retinal PCD periods.
- Recombinant TGF-beta or BMP4 increased apoptosis, with combined treatment showing additive effects, converging at the transcriptional level of TIEG and Gcn5.
Conclusions:
- TGF-beta and BMP4 signaling pathways cooperate in inducing programmed cell death of retinal ganglion cells.
- The interaction occurs at the transcriptional level, not ligand, receptor, or Smad protein level.
- This coordinated action is crucial for regulating cell numbers during retinal development.
More Related Videos
11:48Grafting of Beads into Developing Chicken Embryo Limbs to Identify Signal Transduction Pathways Affecting Gene Expression
Published on: January 17, 2016
09:04Analysis 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
01:16TGF - β Signaling Pathway
01:23Negative Regulator Molecules
01:20The Retinoblastoma Gene
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,...