Expression and functional analysis of novel downstream targets of Hoxa2 and epigenetic regulation of Hoxa2 in the developing mouse

腭裂是人类最常见的先天性出生缺陷之一，发生的频率为1：700至1：1000活产。继发性腭裂可以是单独的出生缺陷(非综合征)，也可以是唇裂或其他综合征的一部分。遗传因素和环境因素在腭裂的发生发展中起着重要作用。最近的研究还表明，在腭裂患者中观察到了广泛的额外影响，例如显著缩短了寿命，增加了所有主要死因的风险。腭裂的影响是多样的和复杂的，对调节腭裂发生的因素还没有完全的了解。次级腭部的发育受到一个复杂的通路网络的调控，这些通路共同作用，严格调控腭部的关键细胞过程，包括细胞生长、细胞死亡和细胞迁移。在小鼠中，胚胎11.5天(E11.5)时，双侧上颌骨第一次发育为上颌突的副产物。然后，货架沿着舌头两侧垂直生长，直到E14.0，之后货架经历快速上升，变得水平朝向舌头上方的另一个。然后，升高的腭架彼此朝向彼此生长，直到每个搁架接触并融合形成次要上颚。

Cleft palate is one of the most common congenital birth defects in humans, occurring with a frequency of 1:700 to 1:1000 live births. A cleft secondary palate can occur as an isolated birth defect (non-syndromic) in conjunction with a cleft lip or as a part of another syndrome. Both genetic and environmental factors play roles in the development of cleft palate. Recent studies also demonstrate a wide range of additional effects observed in individuals with a cleft palate, such as a significantly shorter lifespan with an increased risk for all major causes of death. The effects of cleft palate are diverse and complex, and a complete understanding of the factors in regulating palatogenesis has yet to be achieved. The development of the secondary palate is regulated by a complex network of pathways that work together to tightly regulate critical cellular processes in the palate, including cell growth, cell death, and cell migration. In the mouse, bilateral palate shelves first develop as outgrowths from the maxillary processes at embryonic day 11.5 (E11.5). The shelves then grow vertically down either side of the tongue until E14.0 after which the shelves undergo a rapid elevation to become horizontally oriented towards one another above the tongue. The elevated palatal shelves then grow towards one another until each shelf contacts and fuses to form a secondary palate.