Dong Chunmin, Umar Meenakshi, Bartoletti Garrett, Gahankari Apurva, Fidelak Lauren, He Fenglei
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Gene Expr Patterns. 2019 Dec;34:119060. doi: 10.1016/j.gep.2019.119060. Epub 2019 Jun 19.
Formation of the calvaria is a multi-staged process and is regulated by multiple genetic factors. Disruption of normal calvarial development usually causes craniosynostosis, a prevalent birth defect characterized by premature fusion of calvarial bone. Recent studies have identified mutations of KMT2D allele in patients with craniosynostosis, indicating a potential role for Kmt2d in calvarial development. KMT2D mutations have also been implicated in Kabuki syndrome, which features a distinct facial appearance, skeletal abnormality, growth retardation and intellectual disability. However, the expression pattern of Kmt2d has not been fully elucidated. In the present study we examined the expression pattern of Kmt2d at multiple stages of embryo development in mice, with a focus on the craniofacial tissues. Our in situ hybridization results showed that Kmt2d mRNA is expressed in the developing calvarial osteoblasts, epithelia and neural tissues. Such an expression pattern is in line with the phenotypes of Kabuki syndrome, suggesting that Kmt2d plays an intrinsic role in normal development and homeostasis of these craniofacial tissues.
颅骨的形成是一个多阶段过程，受多种遗传因素调控。正常颅骨发育的破坏通常会导致颅缝早闭，这是一种常见的出生缺陷，其特征是颅骨过早融合。最近的研究在颅缝早闭患者中发现了KMT2D等位基因的突变，表明Kmt2d在颅骨发育中具有潜在作用。KMT2D突变也与歌舞伎综合征有关，该综合征的特征是独特的面部外观、骨骼异常、生长发育迟缓以及智力残疾。然而，Kmt2d的表达模式尚未完全阐明。在本研究中，我们研究了Kmt2d在小鼠胚胎发育多个阶段的表达模式，重点关注颅面部组织。我们的原位杂交结果显示，Kmt2d mRNA在发育中的颅骨成骨细胞、上皮和神经组织中表达。这种表达模式与歌舞伎综合征的表型一致，表明Kmt2d在这些颅面部组织的正常发育和内环境稳定中发挥内在作用。
