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Regulation of limb patterning by extracellular microfibrils.
E Arteaga-Solis1, B Gayraud, S Y Lee
1Brookdale Center, Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
The Journal of Cell Biology
|July 27, 2001
Summary
Fibrillin-2 (Fbn2) deficiency causes syndactyly, a limb defect, by impairing mesenchyme differentiation and interacting with BMP-7 signaling during vertebrate organogenesis.
Area of Science:
- Developmental Biology
- Extracellular Matrix
- Genetics
Background:
- The extracellular microfibril-elastic fiber network is crucial for vertebrate organogenesis.
- Fibrillin-2 (Fbn2) is a key component of microfibrils and elastic fibers.
Purpose of the Study:
- To investigate the role of Fbn2 in vertebrate limb development.
- To elucidate the contribution of the extracellular matrix to organogenesis.
Main Methods:
- Generation of Fbn2-null mice using gene targeting.
- Analysis of limb patterning defects, including syndactyly.
- Investigation of apoptosis and mesenchyme differentiation in affected tissues.
- Assessment of interactions with Bone Morphogenetic Protein (BMP) signaling pathways.
Main Results:
- Fbn2-null mice exhibit bilateral syndactyly, characterized by digit fusion.
- Syndactyly is primarily caused by defective mesenchyme differentiation, not reduced apoptosis.
- Fbn2 deficiency leads to a disorganized extracellular matrix.
- Double heterozygous mice for Fbn2 and Bmp7 display combined phenotypes, indicating functional interaction.
Conclusions:
- Fibrillin-2 is essential for normal limb patterning during vertebrate organogenesis.
- There is a functional interaction between Fbn2-rich microfibrils and BMP-7 signaling in limb development.
- This study reveals an unexpected link between the extracellular matrix and soluble factors in organogenesis.