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Pathogenesis of cleft palate in TGF-beta3 knockout mice
Y Taya1, S O'Kane, M W Ferguson
1Division of Cells, Immunology and Development, School of Biological Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Development (Cambridge, England)
|August 6, 1999
Summary
Transforming growth factor-beta3 (TGF-beta3) is crucial for palatal fusion. Its absence causes cleft palate in mice, but TGF-beta3 treatment can restore fusion by promoting filopodia formation on medial edge epithelial cells.
Area of Science:
- Developmental Biology
- Genetics
- Cell Biology
Background:
- Transforming growth factor-beta3 (TGF-beta3) gene mutations lead to cleft palate in mice.
- TGF-beta3 is normally expressed in medial edge epithelial (MEE) cells of the palatal shelf during embryonic development.
Purpose of the Study:
- To investigate the mechanisms by which TGF-beta3 deficiency causes cleft palate.
- To explore the potential of TGF-beta family members to rescue palatal fusion in vitro.
Main Methods:
- Organ culture of palatal shelves from TGF-beta3 null (-/-) and wild-type (+/+) mouse embryos.
- Paired culture of homologous and heterologous palatal shelves.
- Treatment with recombinant TGF-beta family members (TGF-beta1, TGF-beta2, TGF-beta3) and assessment of fusion.
- Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to analyze MEE cell surface ultrastructure.
Main Results:
- TGF-beta3 null (-/-) palatal shelves failed to fuse in vitro, while wild-type (+/+) and heterozygote (+/-) shelves fused normally.
- Treatment with recombinant TGF-beta3, TGF-beta1, or TGF-beta2 rescued fusion in -/- palatal shelves, with TGF-beta3 being most effective.
- TGF-beta3 deficiency prevented the formation of filopodia-like structures on MEE cells prior to fusion; TGF-beta3 treatment induced these structures in -/- shelves.
Conclusions:
- TGF-beta3 regulates palatal fusion by inducing filopodia on MEE cells, facilitating proper shelf contact.
- Exogenous TGF-beta3 can rescue palatal fusion in null embryos by promoting filopodia formation.
- These findings suggest potential therapeutic strategies for preventing and treating embryonic cleft palate.