Cleft lip and palate are the most common congenital malformations in humans. Using 43 staged human embryos and early fetuses ranging from the 4th to 12th week of development, we investigated the development of the lip and palate in order to provide the basic developmental concepts required for managing these anomalies. The lower lip appeared as bilateral mandibular arches at Carnegie stage 11, and these were completely merged at stage 15. The components of the upper lip, medial nasal prominence and maxillary process, appeared at stage 16, and completely merged at stage 20. The median palatine process appeared at stage 16, and the lateral palatine process, at stage 17. The palatine processes and the nasal septum started to fuse abruptly at stage 23, and from external observation seemed to be fused at the 9th week. However, complete fusion did not take place until the 12th week of development. The tongue was prominent at stage 16, showed differentiation of the muscular tissue at stage 21, and was located superior to the lateral palatine process before stage 23. These results may be used in understanding the different mechanisms present in the formation of various congenital anomalies in this region.
Female ; Gestational Age ; Human ; Lip/embryology* ; Palate/embryology* ; Pregnancy

Cleft lip and/or palate (CL/P) is a common congenital malformation with a complex etiology which is not fully elucidated yet. Epidemiological studies point to different etiologies in the cleft lip and palate subgroups, isolated cleft lip (CL), isolated cleft palate (CP) and combined cleft lip and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed. Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend that future gene expression in CL/P studies should use tissue from the correct embryonic time and place if possible, to overcome the biases in the presented study.
Cleft Lip/*genetics/*immunology ; Cleft Palate/embryology/*genetics/*immunology ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Infant ; Oligonucleotide Array Sequence Analysis ; Osteopontin/*genetics/immunology ; Reverse Transcriptase Polymerase Chain Reaction