Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
Development. 2011 Jan;138(2):339-48. doi: 10.1242/dev.054056.
The pharyngeal apparatus is a transient structure that gives rise to the thymus and the parathyroid glands and also contributes to the development of arteries and the cardiac outflow tract. A typical developmental disorder of the pharyngeal apparatus is the 22q11 deletion syndrome (22q11DS), for which Tbx1 is responsible. Here, we show that Ripply3 can modulate Tbx1 activity and plays a role in the development of the pharyngeal apparatus. Ripply3 expression is observed in the pharyngeal ectoderm and endoderm and overlaps with strong expression of Tbx1 in the caudal pharyngeal endoderm. Ripply3 suppresses transcriptional activation by Tbx1 in luciferase assays in vitro. Ripply3-deficient mice exhibit abnormal development of pharyngeal derivatives, including ectopic formation of the thymus and the parathyroid gland, as well as cardiovascular malformation. Corresponding with these defects, Ripply3-deficient embryos show hypotrophy of the caudal pharyngeal apparatus. Ripply3 represses Tbx1-induced expression of Pax9 in luciferase assays in vitro, and Ripply3-deficient embryos exhibit upregulated Pax9 expression. Together, our results show that Ripply3 plays a role in pharyngeal development, probably by regulating Tbx1 activity.
咽器是一种短暂存在的结构，它可以发育成胸腺和甲状旁腺，也有助于动脉和心流出道的发育。咽器的一种典型发育障碍是 22q11 缺失综合征（22q11DS），其由 Tbx1 负责。在这里，我们表明 Ripply3 可以调节 Tbx1 的活性，并在咽器的发育中发挥作用。Ripply3 在咽外胚层和内胚层中表达，并与 Tbx1 在尾侧咽内胚层中的强表达重叠。Ripply3 在体外的荧光素酶检测中抑制 Tbx1 的转录激活。Ripply3 缺陷小鼠表现出咽衍生物的异常发育，包括胸腺和甲状旁腺的异位形成，以及心血管畸形。与这些缺陷相对应的是，Ripply3 缺陷胚胎表现出尾侧咽器的发育不良。Ripply3 在体外的荧光素酶检测中抑制 Tbx1 诱导的 Pax9 表达，而 Ripply3 缺陷胚胎表现出 Pax9 表达的上调。总之，我们的结果表明，Ripply3 在咽发育中发挥作用，可能是通过调节 Tbx1 的活性。
