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

Hoxa2新下游靶标的表达和功能分析以及Hoxa2在发育小鼠中的表观遗传调控

• 批准号: 171317-2012
• 负责人: Nazarali, Adil
• 金额: $ 2.48万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=593591
• 关键词: Expression; functional; analysis; novel; downstream

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.

腭裂是人类最常见的先天性出生缺陷之一，发生率为1：700至1：1000活产。继发性腭裂可以作为孤立的出生缺陷（非综合征）与唇裂一起发生，也可以作为另一种综合征的一部分发生。遗传和环境因素在腭裂的发生发展中起作用。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，例如寿命显着缩短，所有主要死亡原因的风险增加。腭裂的影响是多样的和复杂的，并在调节腭发育的因素尚未达到一个完整的理解。次级腭的发育受一个复杂的通路网络的调节，这些通路共同作用以严格调节腭中的关键细胞过程，包括细胞生长、细胞死亡和细胞迁移。在小鼠中，双侧腭架首先在胚胎第11.5天（E11.5）从上颌突发育而来。然后，搁架在舌部的任一侧垂直向下生长，直到E14.0，之后搁架经历快速升高，以在舌部上方变为朝向彼此水平定向。然后，升高的腭架朝向彼此生长，直到每个腭架接触并融合以形成次级腭。