Watanabe Y, Duprez D, Monsoro-Burq A H, Vincent C, Le Douarin N M
Institut d'Embryologie Cellulaire et Moléculaire du CNRS et Collège de France, 94736 Nogent-sur-Marne Cedex, France.
Development. 1998 Jul;125(14):2631-9. doi: 10.1242/dev.125.14.2631.
It has previously been shown that the notochord grafted laterally to the neural tube enhances the differentiation of the vertebral cartilage at the expense of the derivatives of the dermomyotome. In contrast, the dorsomedial graft of a notochord inhibits cartilage differentiation of the dorsal part of the vertebra carrying the spinous process. Cartilage differentiation is preceded by the expression of transcription factors of the Pax family (Pax1/Pax9) in the ventrolateral domain and of the Msx family in the dorsal domain. The proliferation and differentiation of Msx-expressing cells in the dorsal precartilaginous domain of the vertebra are stimulated by BMP4, which acts upstream of Msx genes. It has previously been shown that the SHH protein arising from the notochord (and floor plate) is necessary for the survival and further development of Pax1/Pax9-expressing sclerotomal cells. We show here that SHH acts antagonistically to BMP4. SHH-producing cells grafted dorsally to the neural tube at E2 inhibit expression of Bmp4 and Msx genes and also inhibits the differentiation of the spinous process. We present a model that accounts for cartilage differentiation in the vertebra.
先前的研究表明，移植到神经管侧面的脊索会增强椎骨软骨的分化，但代价是生皮节衍生物的分化。相反，脊索的背内侧移植会抑制带有棘突的椎骨背侧部分的软骨分化。软骨分化之前，腹外侧区域会表达Pax家族（Pax1/Pax9）的转录因子，背侧区域会表达Msx家族的转录因子。椎骨背侧软骨前区域中表达Msx的细胞的增殖和分化受到BMP4的刺激，BMP4在Msx基因的上游起作用。先前的研究表明，来自脊索（和底板）的SHH蛋白对于表达Pax1/Pax9的硬骨细胞的存活和进一步发育是必需的。我们在此表明，SHH对BMP4起拮抗作用。在E2时移植到神经管背侧的产生SHH的细胞会抑制Bmp4和Msx基因的表达，也会抑制棘突的分化。我们提出了一个解释椎骨软骨分化的模型。
