Cell behaviour and cleft palate in the mutant mouse, amputated

Area of Science:

• Developmental biology
• Genetics
• Craniofacial development

Background:

• Cleft palate, a common birth defect, typically results from failed palatal shelf elevation or fusion.
• Previous research focused on the critical phases of palatal shelf elevation and fusion.
• The 'amputated' mouse mutant presents a unique model for studying cleft palate origins.

Purpose of the Study:

• To investigate the underlying cause of cleft palate in the 'amputated' mouse mutant.
• To determine if reduced cell proliferation contributes to the observed palatal defect.
• To analyze the behavior of palatal mesenchymal cells in mutant versus normal embryos.

Main Methods:

• Comparative analysis of palatal shelf development in normal and 'amputated' mice from day 12 to 14 post-conception.
• Measurement of cell proliferation (mitotic index) in palatal shelves.
• Scanning electron microscopy of palatal mesenchyme in 12.5 and 14.5-day embryos.

Main Results:

• Cleft palate in 'amputated' mutants is due to a lack of palatal shelf outgrowth between days 12 and 14.
• No significant difference in cell proliferation was found between mutant and normal palatal shelves.
• Mutant palatal mesenchymal cells exhibited clumping and increased cell-to-cell contact compared to normal.

Conclusions:

• Reduced cell proliferation does not explain the failure of palatal outgrowth in 'amputated' mutants.
• Aberrant mesenchymal cell behavior, specifically aggregation due to increased cell adhesion, inhibits palatal outgrowth.
• This abnormal cell behavior is proposed as the primary cause of cleft palate in this mutant model, leading to subsequent failures in elevation and fusion.