Morphogenesis of median facial clefts in mice treated with diazo-oxo-norleucine (DON).

The morphogenesis of median facial clefts induced in mice by treatment with diazo-oxo-norleucine (DON) was studied. Following maternal treatment with 0.4 mg/kg DON on the 11th gestational day, 23.1% of fetuses recovered at the 18th day exhibited median facial clefts, which were characterized by a separation in the midline of normal midfacial components, i.e., the premaxilla, nasal bones, and nasal capsule. Malformed embryos could first be identified grossly 24 hr after DON administration by the presence of an abnormally wide separation between the two narrowed medial nasal processes. Evidence of cellular degeneration was observed in the mesenchyme of the nasal processes of DON-treated embryos 8 and 12 hr after treatment, but little or no pyknotic debris remained at 24 hr post-injection. Loss of cells due to cell death was reflected in decreased cell density observed in all areas of facial mesenchyme examined 24 hr after DON administration. It is suggested that DON-induced median facial clefts may be caused by a reduction in tissue volume, particularly in the midline, or by an interference with normal facial growth resulting in increased facial width and consequent failure of merging of the medial nasal processes.