Sox9 function in craniofacial development and disease

Abstract

Summary: The Sox family of transcriptional regulators has been implicated in the control of a broad array of developmental processes. One member of this family SOX9 was first identified as a candidate gene for campomelic dysplasia (CD), a human syndrome affecting skeletal, and testis development. In these patients most endochondral bones of the face fail to develop resulting in multiple defects such as micrognathia, cleft palate, and facial dysmorphia. In this review we describe Sox9 expression during embryonic development and summarize loss of function experiments in frog, fish, and mouse embryos highlighting the role of Sox9 in regulating morphogenesis of the face. We also discuss the mutations in and around SOX9 responsible for craniofacial defects in CD patients. genesis 49:200-208, 2011. V V C 2011 Wiley-Liss, Inc.

Molecular Mechanisms Regulating Impaired Neurogenesis of Fragile X Syndrome Human Embryonic Stem Cells

“…In addition, we found that SOX9 expression is positively affected by FMRP levels. SOX9 is involved in regulation of cell fate in several lineages: neural tissue [56], including neural crest [25], and glia [57], testis [58], and chondrocytes [59], which are all known to be affected in FXS. Indeed, FXS patients exhibit mental retardation and autism (an effect on the nervous system), macroorchidism (in males, testis), hyperextensible joints (chondrocytes), and stereotypic faces (neural crest).…”

“…In addition, patients with SOX3 deficiency show symptoms similar to those observed in FXS patients, characterized by intellectual disability [23,24]. SOX9 is known to play key roles in neural crest development, chondrogenesis, and testis development [25], which are also affected in FXS individuals. Collectively, these studies, together with our previous findings, hint at a potential role for SOX genes in FXS pathology during human embryonic development.…”

The protein kinase MLTK regulates chondrogenesis by inducing the transcription factor Sox6

“…However, xSox6 function was unknown in Xenopus. Our analysis then shows that xSox6 expression markedly increases in the prospective cartilage at around stage 39, when precartilaginous condensations are occurring (Kerney et al, 2007;Lee and Saint-Jeannet, 2011), and that chondrocyte differentiation is severely inhibited in xSox6-depleted embryos, whereas prior neural crest development is normal. These results indicate that xSox6 is specifically required for chondrocyte differentiation, very similar to xMLTK.…”

“…Our analysis revealed that the expression of chondrocyte markers is first detected in the prospective craniofacial cartilage at stage 39, when precartilaginous condensations are occurring (Kerney et al, 2007;Lee and Saint-Jeannet, 2011). xSox6 expression begins to increase at around stage 35/36 and then markedly increases at stage 39 in the prospective cartilage, while xSox5 and xSox9 are continuously expressed in the neural crest from the neurula stage to the late tailbud stage.…”

“…In Xenopus, although xSox9 has been studied extensively (Spokony et al, 2002;Lee and Saint-Jeannet, 2011), the roles of xSox5 and xSox6 during embryonic development have not been studied. First, we analyzed the expression patterns of xSox5.…”