Sox9 neural crest determinant gene controls patterning and closure of the posterior frontal cranial suture.
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.
Sahar
David E
DE
Department of Surgery, The Children's Surgical Research Program, Stanford University, CA 94305-5148, USA.
Longaker
Michael T
MT
Quarto
Natalina
N
D000818:Animals; D019521:Body Patterning; D002356:Cartilage / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D007150:Immunohistochemistry; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008953:Models, Anatomic; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation
D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; C527933:Sox9 protein, mouse; D014157:Transcription Factors; C113569:fibroblast growth factor 18; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D012313:RNA