Monsoro-Burq A H, Duprez D, Watanabe Y, Bontoux M, Vincent C, Brickell P, Le Douarin N
Institut d'Embryologie Cellulaire et Moléculaire du CNRS et du Collège de France, Nogent-sur-Marne.
Development. 1996 Nov;122(11):3607-16. doi: 10.1242/dev.122.11.3607.
This study first shows a striking parallel between the expression patterns of the Bmp4, Msx1 and Msx2 genes in the lateral ridges of the neural plate before neural tube closure and later on, in the dorsal neural tube and superficial midline ectoderm. We have previously shown that the spinous process of the vertebra is formed from Msx1- and 2-expressing mesenchyme and that the dorsal neural tube can induce the differentiation of subcutaneous cartilage from the somitic mesenchyme. We show here that mouse BMP4- or human BMP2-producing cells grafted dorsally to the neural tube at E2 or E3 increase considerably the amount of Msx-expressing mesenchymal cells which are normally recruited from the somite to form the spinous process of the vertebra. Later on, the dorsal part of the vertebra is enlarged, resulting in vertebral fusion and, in some cases (e.g. grafts made at E3), in the formation of a 'giant' spinous process-like structure dorsally. In strong contrast, BMP-producing cells grafted laterally to the neural tube at E2 exerted a negative effect on the expression of Pax1 and Pax3 genes in the somitic mesenchyme, which then turned on Msx genes. Moreover, sclerotomal cell growth and differentiation into cartilage were then inhibited. Dorsalization of the neural tube, manifested by expression of Msx and Pax3 genes in the basal plate contacting the BMP-producing cells, was also observed. In conclusion, this study demonstrates that differentiation of the ventrolateral and dorsal parts of the vertebral cartilage is controlled by different molecular mechanisms. The former develops under the influence of signals arising from the floor plate-notochord complex. These signals inhibit the development of dorsal subcutaneous cartilage forming the spinous process, which requires the influence of BMP4 to differentiate.
本研究首次表明，在神经管闭合前神经板外侧嵴中以及之后在背侧神经管和浅表中线外胚层中，Bmp4、Msx1和Msx2基因的表达模式之间存在显著的平行关系。我们之前已经表明，椎骨的棘突由表达Msx1和Msx2的间充质形成，并且背侧神经管可以诱导体节间充质分化为皮下软骨。我们在此表明，在E2或E3时背侧移植到神经管的产生小鼠BMP4或人BMP2的细胞，会显著增加通常从体节募集来形成椎骨棘突的表达Msx的间充质细胞的数量。随后，椎骨的背侧部分会扩大，导致椎体融合，并且在某些情况下（例如在E3时进行的移植），在背侧形成一个“巨大的”棘突样结构。形成强烈对比的是，在E2时侧向移植到神经管的产生BMP的细胞，对体节间充质中Pax1和Pax3基因的表达产生负面影响，而Pax1和Pax3基因随后会开启Msx基因。此外，硬骨细胞的生长以及向软骨的分化随后受到抑制。还观察到神经管背化，表现为与产生BMP细胞接触的基板中Msx和Pax3基因的表达。总之，本研究表明椎骨软骨腹侧和背侧部分的分化受不同分子机制的控制。前者在底板 - 脊索复合体产生的信号影响下发育。这些信号抑制形成棘突的背侧皮下软骨的发育，而棘突的发育需要BMP4的影响才能分化。
