[Genetic and experimental approach to bony craniofacial growth: the role of the divergent homeobox gene Msx1].
Tooth agenesis and clef palate are associated to the mutation of the Msx1 homeobox genes, highlighting the pivotal role of homeobox genes during the initial development of the craniofacial skeleton. Msx1 also controls the terminal differentiation of mineralised tissues forming cells. Recently, a Msx1 antisense RNA has been identified which inhibits Msx1 protein expression in odontoblastic cells. In order to investigate the role of Msx1 gene and its antisense RNAs during the late developmental stages of the craniofacial bone formation, the expression pattern of Msx1 protein, sense and antisense transcripts and the aspects of bone growth have been studied in post-natal normal and Msx1 knock-in mutant mice. Msx1 protein was strongly expressed in preosteoblasts of specific bone sites such as the basal mandible. At the same bone sites, bone growth was impaired or markedly decreased in knock-in mice. The comparison between the various expression patterns of Msx1 protein, sense and antisense RNAs suggests that the site-specific action of Msx1 protein on bone growth and craniofacial morphogenesis and that Msx1 protein level could be controlled by the local ratio of Msx1 sense and antisense RNAs. Regarding our experimental data and hypothesis, a clinical study of patients with MSX1 mutation will be performed in order to better characterize the abnormalities of the craniofacial skeleton growth.
Laboratoire de biologie oro-faciale et pathologie, INSERM EMI-U 0110, Université de Paris VII, Institut biomédical des Cordeliers, Paris.
B
B
Vi-Fane
J R
JR
Nefussi
S
S
Orestes-Cardoso
D
D
Hotton
B
B
Robert
C
C
Chabre
A
A
Berdal
J L
JL
Davideau
D000818:Animals; D019465:Craniofacial Abnormalities / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051957:MSX1 Transcription Factor; D008445:Maxillofacial Development / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016372:RNA, Antisense; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D016372:RNA, Antisense; D014157:Transcription Factors