Sox9 neural crest determinant gene controls patterning and closure of the posterior frontal cranial suture

Abstract

Cranial suture development involves a complex interaction of genes and tissues derived from neural crest cells (NCC) and paraxial mesoderm. In mice, the posterior frontal (PF) suture closes during the first month of life while other sutures remain patent throughout the life of the animal. Given the unique NCC origin of PF suture complex (analogous to metopic suture in humans), we performed quantitative real-time PCR and immunohistochemistry to study the expression pattern of the NCC determinant gene Sox9 and select markers of extracellular matrix. Our results indicated a unique up-regulated expression of Sox9, a regulator of chondrogenesis, during initiation of PF suture closure, along with the expression of specific cartilage markers (Type II Collagen and Type X Collagen), as well as cartilage tissue formation in the PF suture. This process was followed by expression of bone markers (Type I Collagen and Osteocalcin), suggesting endochondral ossification. Moreover, we studied the effect of haploinsufficiency of the NCC determinant gene Sox9 in the NCC derived PF suture complex. A decrease in dosage of Sox9 by haploinsufficiency in NCC-derived tissues resulted in delayed PF suture closure. These results demonstrate a unique development of the PF suture complex and the role of Sox9 as an important contributor to timely and proper closure of the PF suture through endochondral ossification.

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

“…Several Sox factors are known to play critical roles in craniofacial and limb skeletogenesis and are good candidates to regulate Tcfap2a (Bi et al, 1999(Bi et al, , 2001Smits et al, 2001;Sock et al, 2004). The Group E factor, Sox9, is an enticing candidate, given both its role in chondrogenesis and its responsiveness to retinoic acid (Bi et al, 1999(Bi et al, , 2001Sekiya et al, 2000;Akiyama et al, 2002Akiyama et al, , 2004MoriAkiyama et al, 2003;Sahar et al, 2005), an agent known to alter AP-2␣ expression in vitro and in vivo (Williams et al, 1988;Lü scher et al, 1989;Philipp et al, 1994;Shen et al, 1997). Another Group E candidate, Sox8, is expressed coincident with Tcfap2a in the face and limbs (Wegner, 1999;Schepers et al, 2000).…”

Metopismo: Bases Morfológicas, Implicancias Clínicas y Reporte de Caso

“…Sin embargo, en la actualidad se sabe que el desarrollo craneofacial normal depende principalmente de la contribución precisa de tejido derivado de las células de la cresta neural y mesodermo paraxial, junto a una regulación controlada por genes específicos. Una aberración en cualquiera de los niveles de control podría llevar al cierre prematuro de suturas (craneosinostosis) o retraso en el cierre de sutura, conocido como metopismo (Opperman, 2000;Rice et al, 2003;Sahar et al, 2005).…”

Craniomaxillofacial Sources of Mesenchymal Stem Cells: A Brief Review

“…By contrast, the sagittal suture, along with all others remains patent throughout adulthood [45] . Suturederived mesenchymal stromal cells (SMC) have been isolated from each of these midline cranial sutures and have found to have distinctly different properties, as discussed below.…”