Related Experiment Videos
Nell-1 induces acrania-like cranioskeletal deformities during mouse embryonic development
Xinli Zhang1, Catherine M Cowan, Xinquan Jiang
1Dental and Craniofacial Research Institute, University of California, Los Angeles, CA 90095, USA.
Summary
Overexpression of NELL-1 causes craniosynostosis and neural tube defects in mice by inducing massive apoptosis, particularly involving the Fas/Fas-L pathway. This highlights NELL-1
Area of Science:
- Developmental biology
- Genetics
- Cell biology
Background:
- NELL-1 is a novel molecule overexpressed in craniosynostosis (CS).
- NELL-1 overexpression in transgenic mice causes premature suture closure.
- Cellular effects include induced osteoblast differentiation and apoptosis.
Purpose of the Study:
- To investigate craniofacial and neural tube defects (NTDs) in Nell-1 overexpressing mice during embryonic development.
- To elucidate the cellular mechanisms underlying these defects, focusing on apoptosis and the Fas/Fas-L pathway.
Main Methods:
- Analysis of transgenic mice during embryonic development (E15.5) and postnatally.
- Histological examination of craniofacial structures and neural tissues.
- In vitro studies using primary chondrocytes transduced with AdNell-1.
Main Results:
- Nell-1 overexpression induced acrania in mouse embryos at E15.5 via massive apoptosis in calvarial osteoblasts and neural cells.
- Increased Fas and Fas-L production was associated with induced apoptosis.
- Transgenic mice showed chondrocranium distortion, premature chondrocyte hypertrophy, and apoptosis.
Conclusions:
- NELL-1 overexpression can induce craniofacial anomalies and neural tube defects during embryonic development.
- Massive apoptosis, potentially mediated by the Fas/Fas-L signaling pathway, is a key mechanism.
- Findings suggest a significant role for NELL-1 in craniofacial and neural development.