Fabik Jaroslav, Psutkova Viktorie, Machon Ondrej
Department of Developmental Biology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.
Department of Cell Biology, Faculty of Science, Charles University, Prague, Czechia.
Front Cell Dev Biol. 2022 Sep 28;10:951063. doi: 10.3389/fcell.2022.951063. eCollection 2022.
A vertebrate skull is composed of many skeletal elements which display enormous diversity of shapes. Cranial bone formation embodies a multitude of processes, i.e., epithelial-mesenchymal induction, mesenchymal condensation, and endochondral or intramembranous ossification. Molecular pathways determining complex architecture and growth of the cranial skeleton during embryogenesis are poorly understood. Here, we present a model of the hyoid apparatus development in Wnt1-Cre2-induced conditional knock-out (cKO) mice. cKO embryos develop an aberrant hyoid apparatus-a complete skeletal chain from the base of the neurocranium to lesser horns of the hyoid, resembling extreme human pathologies of the hyoid-larynx region. We examined key stages of hyoid skeletogenesis to obtain a complex image of the hyoid apparatus formation. Lack of resulted in ectopic loci of mesenchymal condensations, ectopic cartilage and bone formation, disinhibition of skeletogenesis, and elevated proliferation of cartilage precursors. We presume that all these mechanisms contribute to formation of the aberrant skeletal chain in the hyoid region. Moreover, cKO embryos exhibit severely reduced expression of PBX1 and HAND2 in the hyoid region. Altogether, MEIS2 in conjunction with PBX1 and HAND2 affects mesenchymal condensation, specification and proliferation of cartilage precursors to ensure development of the anatomically correct hyoid apparatus.
脊椎动物的头骨由许多骨骼元素组成，这些元素呈现出极其多样的形状。颅骨形成体现了多种过程，即上皮-间充质诱导、间充质凝聚以及软骨内或膜内成骨。在胚胎发育过程中，决定颅骨架复杂结构和生长的分子途径尚不清楚。在此，我们展示了Wnt1-Cre2诱导的条件性敲除（cKO）小鼠舌骨器发育的模型。cKO胚胎发育出异常的舌骨器——从脑颅底部到舌骨小角的完整骨骼链，类似于人类舌骨-喉部区域的极端病理情况。我们检查了舌骨骨骼发生的关键阶段，以获得舌骨器形成的复杂图像。[此处原文缺失关键信息]的缺失导致间充质凝聚的异位位点、异位软骨和骨形成、骨骼发生的去抑制以及软骨前体细胞增殖增加。我们推测所有这些机制都有助于舌骨区域异常骨骼链的形成。此外，cKO胚胎在舌骨区域表现出PBX1和HAND2的表达严重降低。总之，MEIS2与PBX1和HAND2共同影响间充质凝聚、软骨前体细胞的特化和增殖，以确保解剖学上正确的舌骨器的发育。
