Carroll Shannon H, Schafer Sogand, Richman Ariella S, Tsay Lisa, Wang Peng, Ahsan Mian Umair, Wang Kai, Liao Eric C
Center for Craniofacial Innovation, Division of Plastic and Reconstructive Surgery, Department of Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Shriners Hospital for Children, Tampa, FL, USA.
medRxiv. 2025 Apr 3:2025.04.02.25325077. doi: 10.1101/2025.04.02.25325077.
The pituitary gland produces several hormones that regulate growth, metabolism, stress response, reproduction, and homeostasis. Congenital hypopituitarism is a deficiency in one or more pituitary hormones and encompasses a spectrum of clinical conditions. The pituitary has a complex embryonic origin with the oral ectoderm contributing the anterior lobe, and the neural ectoderm generating the posterior lobe. Pituitary abnormalities and growth deficiencies are associated with cleft palate however the developmental genetic connection between pituitary and orofacial cleft malformations remains to be determined. The epithelial RNA splicing regulators and are required for orofacial development in zebrafish, mice, and humans, and loss of function of these genes results in a cleft palate. Here we present a detailed developmental analysis of the genetic requirement for in pituitary morphogenesis in mouse and zebrafish. Further, we describe a patient with cleft palate and hypopituitarism that harbors a nucleotide variant in the RNA binding domain of . The discovery of this key function for in pituitary formation has significant fundamental and clinical implications for understanding congenital hypopituitarism and craniofacial anomalies.
垂体产生多种调节生长、代谢、应激反应、生殖和体内平衡的激素。先天性垂体功能减退是一种或多种垂体激素缺乏的病症，涵盖一系列临床情况。垂体具有复杂的胚胎起源，口腔外胚层形成前叶，神经外胚层产生后叶。垂体异常和生长缺陷与腭裂有关，然而垂体与口面部裂畸形之间的发育遗传联系仍有待确定。上皮RNA剪接调节因子 和 在斑马鱼、小鼠和人类的口面部发育中是必需的，这些基因功能丧失会导致腭裂。在这里，我们对小鼠和斑马鱼垂体形态发生中 基因需求进行了详细的发育分析。此外，我们描述了一名患有腭裂和垂体功能减退的患者，其 在RNA结合结构域存在核苷酸变异。 在垂体形成中的这一关键功能的发现，对于理解先天性垂体功能减退和颅面异常具有重要的基础和临床意义。
