Ibarra Beatriz A, Machen Cody, Atit Radhika P
Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
J Dev Biol. 2021 Jun 27;9(3):23. doi: 10.3390/jdb9030023.
Wnt signaling regulates cell fate decisions in diverse contexts during development, and loss of Wnt signaling in the cranial mesenchyme results in a robust and binary cell fate switch from cranial bone to ectopic cartilage. The Extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and Wnt signaling pathways are activated during calvarial osteoblast cell fate selection. Here, we test the hypothesis that ERK signaling is a mediator of Wnt-dependent cell fate decisions in the cranial mesenchyme. First, we show that loss of 2 in the cranial mesenchyme results in a diminished domain of osteoblast marker expression and increased expression of cartilage fate markers and ectopic cartilage formation in the frontal bone primordia. Second, we show that mesenchyme Wnt/β-catenin signaling and are required for ERK activation in calvarial osteoblasts. Third, we demonstrate that Wnt and ERK signaling pathways function together to repress SOX9 expression in mouse cranial mesenchyme. Our results demonstrate an interaction between the Wnt and ERK signaling pathways in regulating lineage selection in a subset of calvarial cells and provide new insights into Wnt-dependent cell fate decisions.
Wnt信号通路在发育过程中的多种情况下调节细胞命运决定，颅间充质中Wnt信号通路的缺失会导致从颅骨到异位软骨的强大且二元的细胞命运转变。在颅盖成骨细胞命运选择过程中，细胞外信号调节蛋白激酶1和2（ERK1/2）以及Wnt信号通路被激活。在此，我们检验ERK信号是颅间充质中Wnt依赖的细胞命运决定的介导因子这一假说。首先，我们表明颅间充质中2的缺失导致成骨细胞标志物表达域减少，软骨命运标志物表达增加以及额骨原基中异位软骨形成。其次，我们表明间充质Wnt/β-连环蛋白信号通路以及是颅盖成骨细胞中ERK激活所必需的。第三，我们证明Wnt和ERK信号通路共同作用以抑制小鼠颅间充质中SOX9的表达。我们的结果证明了Wnt和ERK信号通路在调节颅盖细胞亚群中的谱系选择方面的相互作用，并为Wnt依赖的细胞命运决定提供了新见解。
