Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, School of Medicine, Stanford, CA, USA.
Cells Tissues Organs. 2010;191(5):401-13. doi: 10.1159/000272318. Epub 2009 Dec 24.
Cranial suture development involves coordinated expression of multiple genes and tissue contribution from neural crest cells and paraxial mesoderm for timely sutural morphogenesis. Transcription factors, growth factors, and neural crest determinant genes play critical roles in calvarial growth ensuring normal development of the underlying brain. In vitro studies have implicated cell-cell adhesion molecules as a driving force behind suture closure. We performed cDNA microarray to study differential expression of adhesion molecules during the timing of suture closure in a mouse model where only the posterior frontal (PF) suture closes. Our results indicate increased expression of E-cadherin during the period of PF suture closure. Quantitative RT-PCR analysis of E- and N-cadherin in PF closing suture revealed a biphasic expression of N-cadherin, the first phase coinciding with cellular condensation preceding chondrogenesis followed by a second phase coinciding with E-cadherin co-expression and suture closure. Furthermore, expression analysis of the N-cadherin and E-cadherin transcriptional repressors Wnt7a and Snail indicate a specific temporal regulation of these genes, suggesting their potential role as regulators of both E- and N-cadherin during the PF suture development and closure. Finally, given the in vitro evidence of fibroblast growth factor (FGF)-2 as a potential regulator of E- and N-cadherin we investigated the expression of E-cadherin during PF suture closure in Fgf-2 deficient mice. In contrast to in vitrodata previously reported, E-cadherin expression is normal in these animals, and PF suture closure occurs properly, probably due to potential redundancy of FGF ligands ensuring normal temporal expression of E-cadherin and PF suture closure.
颅缝发育涉及多个基因的协调表达，以及神经嵴细胞和轴旁中胚层对缝间形态发生的组织贡献。转录因子、生长因子和神经嵴决定基因在颅骨生长中发挥着重要作用，以确保大脑的正常发育。体外研究表明，细胞-细胞黏附分子是缝闭合的驱动力。我们进行了 cDNA 微阵列分析，以研究在仅后额缝（PF）闭合的小鼠模型中，缝闭合过程中黏附分子的差异表达。我们的结果表明，在 PF 缝闭合期间，E-钙黏蛋白的表达增加。对 PF 闭合缝中 E-和 N-钙黏蛋白的定量 RT-PCR 分析显示，N-钙黏蛋白呈双峰表达，第一相与软骨形成前的细胞凝聚相一致，随后第二相与 E-钙黏蛋白共表达和缝闭合相一致。此外，对 N-钙黏蛋白和 E-钙黏蛋白转录抑制因子 Wnt7a 和 Snail 的表达分析表明，这些基因的表达具有特定的时间调节，表明它们在 PF 缝发育和闭合过程中作为 E-和 N-钙黏蛋白的潜在调节剂的作用。最后，鉴于体外证据表明成纤维细胞生长因子（FGF）-2 可能是 E-和 N-钙黏蛋白的潜在调节剂，我们研究了在 Fgf-2 缺陷小鼠中 PF 缝闭合过程中 E-钙黏蛋白的表达。与之前报道的体外数据相反，这些动物的 E-钙黏蛋白表达正常，PF 缝闭合正常发生，这可能是由于 FGF 配体的潜在冗余，确保了 E-钙黏蛋白和 PF 缝闭合的正常时间表达。
