Department of Genetics, University of Georgia, Athens, GA 30602, USA.
Dev Biol. 2010 Mar 1;339(1):141-54. doi: 10.1016/j.ydbio.2009.12.026. Epub 2010 Jan 4.
The thymus and parathyroids are pharyngeal endoderm-derived organs that develop from common organ primordia, which undergo a series of morphological events resulting in separate organs in distinct locations in the embryo. Previous gene expression and functional analyses have suggested a role for BMP4 signaling in early thymus organogenesis. We have used conditional deletion of Bmp4 or Alk3 from the pharyngeal endoderm and/or the surrounding mesenchyme using Foxg1-Cre, Wnt1-Cre or Foxn1-Cre. Deleting Bmp4 from both neural crest cells (NCC) and early endoderm-derived epithelial cells in Foxg1-Cre;Bmp4 conditional mutants resulted in defects in thymus-parathyroid morphogenesis. Defects included reduced condensation of mesenchymal cells around the epithelium, partial absence of the thymic capsule, a delay in thymus and parathyroid separation, and failed or dramatically reduced organ migration. Patterning of the primordia and initial organ differentiation were not affected in any of the mutants. Deleting Bmp4 from NCC-derived mesenchyme or differentiating thymic epithelial cells (TECs) had no effects on thymus-parathyroid development, while loss of Alk3 from either neural crest cells or TECs resulted in only a mild thymic hypoplasia. these results show that the processes of cell specification and morphogenesis during thymus-parathyroid development are independently controlled, and suggest a specific temporal and spatial role for BMP4-mediated epithelial-mesenchymal interactions during early thymus and parathyroid morphogenesis.
胸腺和甲状旁腺是咽内胚层衍生的器官,它们由共同的器官原基发育而来,经历了一系列形态发生事件,导致胚胎中不同位置的独立器官。先前的基因表达和功能分析表明,BMP4 信号在早期胸腺器官发生中起作用。我们使用 Foxg1-Cre、Wnt1-Cre 或 Foxn1-Cre 从咽内胚层和/或周围的间充质中条件性缺失 Bmp4 或 Alk3。在 Foxg1-Cre 中从神经嵴细胞 (NCC) 和早期内胚层衍生的上皮细胞中缺失 Bmp4 的条件突变体导致胸腺-甲状旁腺形态发生缺陷。缺陷包括围绕上皮细胞的间充质细胞的凝聚减少、胸腺囊的部分缺失、胸腺和甲状旁腺分离延迟、器官迁移失败或显著减少。在任何突变体中,原基的模式形成和初始器官分化都没有受到影响。从 NCC 衍生的间充质或分化的胸腺上皮细胞 (TEC) 中缺失 Bmp4 对胸腺-甲状旁腺发育没有影响,而从神经嵴细胞或 TEC 中缺失 Alk3 仅导致轻微的胸腺发育不全。这些结果表明,胸腺-甲状旁腺发育过程中的细胞特化和形态发生过程是独立控制的,并表明在早期胸腺和甲状旁腺形态发生中,BMP4 介导的上皮-间充质相互作用具有特定的时空作用。