Figure 1. Children with orofacial clefts. (a) Cleft lip is a unilateral or bilateral gap in the upper lip and upper jaw. (b) Cleft palate is a gap in the roof of the mouth. Permission given from University of Iowa Hospitals and Clinics-Dept of Paediatrics provided by Professor Jeff Murray, (a) Parental consent from Antonia Cuizon and (b) Jerard Magisanua's consent.

Figure 2. Schematic diagrams depicting human craniofacial development and formation of the secondary palate. (a) By the fourth week of embryonic development, neural crest cells have migrated into the craniofacial region to form the frontonasal prominence, paired maxillary processes and the paired mandibular processes. (b) Formation of the nasal pits by the fifth week of embryogenesis divides the frontonasal prominence into paired medial and lateral nasal processes. (c) By the end of the sixth week of embryonic development, the medial nasal processes have merged with one another and with the maxillary processes to form the upper lip and primary palate, whereas the lateral nasal processes form the alae of the nose. The mandibular processes fuse together to form the lower jaw. (d) The secondary palate develops from the maxillary processes as bilateral outgrowths which grow vertically down the side of the tongue during the sixth week of embryogenesis. (e) During the seventh week of embryonic development, the palatal shelves elevate to a horizontal position above the tongue, make contact with one another and begin to fuse. (f) Fusion of the secondary palatal shelves with one another and with the primary palate and nasal septum is completed by the tenth week of embryogenesis.

Figure 3. Scanning electron microscopy showing murine craniofacial development. (a) At E9.5, the frontonasal process (fnp) and the paired maxillary (mx) and mandibular (mnd) processes form as the result of migration of cranial neural crest cell, which delaminate from the neural folds, into the developing facial complex. (b) Formation of the nasal pits (np) at E10.5 divides the frontonasal process into the paired medial (mnp) and lateral (lnp) nasal processes. (c) During E11.5, the medial and lateral nasal processes grow sufficiently to surround the nasal pit and to make contact with the maxillary processes. The mandibular processes come together and fuse in the midline. (d) By E12.5, fusion of the medial nasal processes with the maxillary processes and the lateral nasal processes completes the formation of the upper lip.

Figure 4. Whole-mount in situ hybridisation showing the expression of key signalling molecules important for primary palate development. (a) Bmp4 and (b) Msx1 are expressed in the nasal processes, maxillary processes and mandibular processes. (c) Wnt9b is expressed in the epithelia covering the nasal processes and the maxillary and mandibular processes. (d) Fgf8 expression is restricted to the epithelia surrounding the nasal pit and the epithelia covering the oral surface of the medial nasal processes and maxillary and mandibular processes.

Figure 5. Scanning electron microscopy and histological analysis showing murine secondary palate development. (a and d) At E13.5, the palatal shelves (p), which have grown out from the maxillary processes, are in a vertical position down the side of the tongue (t). (b and e) The palatal shelves elevate into a vertical position above the tongue at E14.0. (c and f) During E14.5 the opposing palatal shelves fuse in the midline to form separate oral and nasal cavities.