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BMP and FGF regulate the development of EGF-responsive neural progenitor cells
1Department of Neurobiology and Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, W1454 Biomedical Science Tower, Pittsburgh, PA 15261, USA. lillien+@pitt.edu
Development (Cambridge, England)
|October 25, 2000
Summary
Cell-cell signaling regulates neural progenitor development. Bone morphogenetic protein 4 (BMP4) delays epidermal growth factor receptor (EGFR) signaling changes, while fibroblast growth factor 2 (FGF2) promotes it, balancing progenitor cell timing.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Signaling
Background:
- Temporal regulation of progenitor cell responses to extrinsic signals is crucial for development.
- Epidermal growth factor receptors (EGFRs) expression increases during rodent central nervous system (CNS) development, enabling multipotent stem cell responsiveness to EGF.
- Mechanisms governing these temporal changes in progenitor cell responses remain largely unknown.
Purpose of the Study:
- To investigate the mechanisms controlling temporal changes in neural progenitor cell responsiveness to extrinsic signals.
- To elucidate the role of cell-cell signaling in regulating EGFR expression and EGF responsiveness during embryonic CNS development.
Main Methods:
- Utilized explant and aggregate cultures of embryonic cortex.
- Co-cultured younger and older cortical cells.
- Administered exogenous BMP4 and FGF2.
- Employed viral transduction to express dominant-negative BMP receptor (dnBMPR1B) in progenitors.
Main Results:
- Co-culture with younger cortical cells delayed the development of EGF-responsive stem cells.
- Exogenous BMP4 mimicked the effect of younger cells, reversibly inhibiting EGFR expression and responsiveness.
- Blocking BMP receptors accelerated EGFR signaling changes, indicating a non-cell-autonomous inhibitory role for BMP.
- FGF2 antagonized the inhibitory effects of younger cells and BMP4, suggesting it promotes EGF-responsive stem cell development.
Conclusions:
- Cell-cell signaling, specifically involving BMP and FGF pathways, regulates the temporal acquisition of EGF responsiveness in neural progenitor cells.
- A balance between antagonistic extrinsic signals (BMP and FGF) governs the intrinsic temporal changes in neural progenitor cell properties.
- These findings provide insights into the regulatory mechanisms underlying neurodevelopmental timing.