Section of Molecular Craniofacial Embryology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Sci Rep. 2021 Jan 22;11(1):2092. doi: 10.1038/s41598-021-81434-x.
Neural crest cells (NCCs) give rise to various tissues including neurons, pigment cells, bone and cartilage in the head. Distal-less homeobox 5 (Dlx5) is involved in both jaw patterning and differentiation of NCC-derivatives. In this study, we investigated the differentiation potential of head mesenchyme by forcing Dlx5 to be expressed in mouse NCC (NCC). In NCC mice, differentiation of dermis and pigment cells were enhanced with ectopic cartilage (ec) and heterotopic bone (hb) in different layers at the cranial vertex. The ec and hb were derived from the early migrating mesenchyme (EMM), the non-skeletogenic cell population located above skeletogenic supraorbital mesenchyme (SOM). The ec developed within Foxc1-dura mater with increased PDGFRα signalling, and the hb formed with upregulation of BMP and WNT/β-catenin signallings in Dermo1-dermal layer from E11.5. Since dermal cells express Runx2 and Msx2 in the control, osteogenic potential in dermal cells seemed to be inhibited by an anti-osteogenic function of Msx2 in normal context. We propose that, after the non-skeletogenic commitment, the EMM is divided into dermis and meninges by E11.5 in normal development. Two distinct responses of the EMM, chondrogenesis and osteogenesis, to Dlx5-augmentation in the NCC strongly support this idea.
神经嵴细胞(NCC)产生各种组织,包括神经元、色素细胞、头部的骨骼和软骨。远端同源盒 5(Dlx5)参与颌骨形态发生和 NCC 衍生物的分化。在这项研究中,我们通过迫使 Dlx5 在小鼠 NCC(NCC)中表达来研究头部间质的分化潜力。在 NCC 小鼠中,颅顶异位软骨(ec)和异位骨(hb)在不同层中增强了真皮和色素细胞的分化。ec 和 hb 来源于早期迁移的间质(EMM),即位于骨骼生成超眶间间质(SOM)上方的非骨骼生成细胞群体。ec 在 Foxc1-硬脑膜内发育,PDGFRα 信号增加,hb 在 E11.5 时 Dermo1-真皮层中 BMP 和 WNT/β-catenin 信号上调形成。由于在对照中真皮细胞表达 Runx2 和 Msx2,因此真皮细胞的成骨潜能似乎被正常情况下 Msx2 的抗成骨功能抑制。我们提出,在非骨骼生成后,EMM 在正常发育中通过 E11.5 分为真皮和脑膜。EMM 对 Dlx5 增强的两种不同反应,软骨生成和成骨,强烈支持这一观点。