Hand Arthur R, Abramson Cailyn X G, Dressler Keith A
Department of Craniofacial Sciences, University of Connecticut School of Dental Medicine, Farmington, Connecticut, USA.
J Anat. 2024 Feb;244(2):343-357. doi: 10.1111/joa.13964. Epub 2023 Oct 13.
Tlx1 encodes a transcription factor expressed in several craniofacial structures of developing mice. The role of Tlx1 in salivary gland development was examined using morphological and immunohistochemical analyses of Tlx1 null mice. Tlx1 is expressed in submandibular and sublingual glands but not parotid glands of neonatal and adult male and female C57Bl/6J (Tlx1 ) mice. TLX1 protein was localized to the nuclei of terminal tubule cells, developing duct cells and mesenchymal cells in neonatal submandibular and sublingual glands, and to nuclei of duct cells and connective tissue cells in adult glands. Occasionally, TLX1 was observed in nuclei of epithelial cells in or adjacent to the acini. Submandibular glands were smaller and sublingual glands were larger in size in mutant mice (Tlx1 ) compared to wild-type mice. Differentiation of terminal tubule and proacinar cells of neonatal Tlx1 submandibular glands was abnormal; expression of their characteristic products, submandibular gland protein C and parotid secretory protein, respectively, was reduced. At 3 weeks postnatally, terminal tubule cells at the acinar-intercalated duct junction were poorly developed or absent in Tlx1 mice. Granular convoluted ducts in adult mutant mice were decreased, and epidermal growth factor and nerve growth factor expression were reduced. Along with normal acinar cell proteins, adult acinar cells of Tlx1 mice continued to express neonatal proteins and expressed parotid proteins not normally present in submandibular glands. Sublingual gland mucous acinar and serous demilune cell differentiation were altered. Tlx1 is necessary for proper differentiation of submandibular and sublingual gland acinar cells, and granular convoluted ducts. The mechanism(s) underlying Tlx1 regulation of salivary gland development and differentiation remains unknown.
Tlx1编码一种在发育中小鼠的多个颅面结构中表达的转录因子。利用Tlx1基因敲除小鼠的形态学和免疫组织化学分析，研究了Tlx1在唾液腺发育中的作用。在新生和成年雄性及雌性C57Bl/6J（Tlx1⁻/⁻）小鼠的下颌下腺和舌下腺中表达Tlx1，但在腮腺中不表达。TLX1蛋白定位于新生下颌下腺和舌下腺的终末小管细胞、发育中的导管细胞和间充质细胞的细胞核，以及成年腺体的导管细胞和结缔组织细胞的细胞核。偶尔，在腺泡内或其附近的上皮细胞核中也观察到TLX1。与野生型小鼠相比，突变小鼠（Tlx1⁻/⁻）的下颌下腺较小，舌下腺较大。新生Tlx1⁻/⁻下颌下腺的终末小管和前腺泡细胞分化异常；它们各自特征性产物下颌下腺蛋白C和腮腺分泌蛋白的表达降低。出生后3周，Tlx1⁻/⁻小鼠腺泡-闰管连接处的终末小管细胞发育不良或缺失。成年突变小鼠的颗粒曲管减少，表皮生长因子和神经生长因子表达降低。除了正常的腺泡细胞蛋白外，Tlx1⁻/⁻小鼠的成年腺泡细胞继续表达新生蛋白，并表达下颌下腺通常不存在的腮腺蛋白。舌下腺黏液腺泡和浆液半月细胞的分化发生改变。Tlx1是下颌下腺和舌下腺腺泡细胞以及颗粒曲管正常分化所必需的。Tlx1调节唾液腺发育和分化的潜在机制仍不清楚。
