(55) The Role of SATB2 in Craniofacial Development and Odontogenesis: Insights from Mouse Models and Human Patients

Abstract: Congenital orofacial abnormalities, such as jaw hypoplasia or tooth agenesis, can result from either multifactorial causes or single-gene mutations. Disruptions in genes that regulate normal tissue growth and development may lead to uncontrolled cell proliferation, a key feature of craniofacial development. One candidate gene implicated in these processes is SATB2, a molecule within the BMP pathway that plays a crucial role in regulating various transcription factors during both early embryogenesis and later stages of cell differentiation.
We analyzed SATB2 expression in craniofacial regions along the rostro-caudal axis, observing stronger expression in anterior areas in mice. Additionally, SATB2-positive cells were detected in the mesenchyme surrounding the developing molars and within the forming palatal shelves of mouse embryos. To investigate the potential role of SATB2 in orofacial development, we examined SATB2-deficient mice, which exhibited abnormal craniofacial patterning, including mandibular shortening, cleft palate, incisor hypoplasia and ectopic molar formation.
A similar phenotype has been reported in individuals with SATB2-associated syndrome (SAS, also known as Glass syndrome). We examined two families with probands presenting severe craniofacial abnormalities, including mandibular hypoplasia, oligodontia, significant intellectual disability, and motor difficulties. In the first family, we identified a large heterozygous chromosomal deletion, GRCh37/hg19 2q32.2-33.1 (chr2:189741442-199706840), in the proband, while no pathogenic variants were detected in other family members (parents and two siblings). This deletion includes the SATB2 gene, consistent with the Glass syndrome phenotype. In the second analyzed family, the affected proband carried a heterozygous SATB2 mutation (NM_001172509.2:c.1569G>A; p.(Trp523Ter), exhibiting a similar craniofacial phenotype but with a milder intellectual disability. Both parents had a normal clinical presentation and did not carry pathogenic SATB2 variants.
Together, these findings enhance our understanding of the molecular basis of orofacial defects. However, further research is needed to clarify the precise role of SATB2 in odontogenesis and to gain deeper insights into the molecular pathways regulating tooth development and associated dental anomalies.
This project was support by the Ministry of Health of the Czech Republic, grant no. NW24-10-00204.