Wu Bo-Tsung, Wen Shih-Hsien, Hwang Sheng-Ping L, Huang Chang-Jen, Kuan Yung-Shu
Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, Taiwan Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan.
J Cell Sci. 2015 Jun 15;128(12):2328-39. doi: 10.1242/jcs.167403. Epub 2015 May 1.
Wnts and Fgfs regulate various tissues development in vertebrates. However, how regional Wnt or Fgf activities are established and how they interact in any given developmental event is elusive. Here, we investigated the Wnt-mediated craniofacial cartilage development in zebrafish and found that fgf3 expression in the pharyngeal pouches is differentially reduced along the anteroposterior axis in wnt5b mutants and wntless (wls) morphants, but its expression is normal in wnt9a and wnt11 morphants. Introducing fgf3 mRNAs rescued the cartilage defects in Wnt5b- and Wls-deficient larvae. In wls morphants, endogenous Wls expression is not detectable but maternally deposited Wls is present in eggs, which might account for the lack of axis defects in wls morphants. Secretion of endogenous Wnt5b but not Wnt11 was affected in the pharyngeal tissue of Wls morphants, indicating that Wls is not involved in every Wnt secretion event. Furthermore, cell proliferation but not apoptosis in the developing jaw was affected in Wnt5b- and Wls-deficient embryos. Therefore, Wnt5b requires Wls for its secretion and regulates the proliferation of chondrogenic cells through fine-tuning the expression of fgf3 during jaw cartilage development.
Wnt和Fgf调节脊椎动物的各种组织发育。然而，区域Wnt或Fgf活性是如何建立的，以及它们在任何特定发育事件中如何相互作用尚不清楚。在这里，我们研究了斑马鱼中Wnt介导的颅面软骨发育，发现咽囊中fgf3的表达在wnt5b突变体和wntless（wls）突变体中沿前后轴差异降低，但其在wnt9a和wnt11突变体中的表达正常。引入fgf3 mRNA可挽救Wnt5b和Wls缺陷幼虫的软骨缺陷。在wls突变体中，内源性Wls表达无法检测到，但卵中存在母源性沉积的Wls，这可能解释了wls突变体中缺乏轴缺陷的原因。Wls突变体的咽组织中内源性Wnt5b的分泌受到影响，但Wnt11不受影响，这表明Wls并不参与每个Wnt分泌事件。此外，Wnt5b和Wls缺陷胚胎中发育中的颌骨中的细胞增殖受到影响，而细胞凋亡不受影响。因此，Wnt5b的分泌需要Wls，并通过在颌骨软骨发育过程中微调fgf3的表达来调节软骨形成细胞的增殖。
