Diez del Corral Ruth, Olivera-Martinez Isabel, Goriely Anne, Gale Emily, Maden Malcolm, Storey Kate
Division of Cell and Developmental Biology, Faculty of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom.
Neuron. 2003 Sep 25;40(1):65-79. doi: 10.1016/s0896-6273(03)00565-8.
Vertebrate body axis extension involves progressive generation and subsequent differentiation of new cells derived from a caudal stem zone; however, molecular mechanisms that preserve caudal progenitors and coordinate differentiation are poorly understood. FGF maintains caudal progenitors and its attenuation is required for neuronal and mesodermal differentiation and to position segment boundaries. Furthermore, somitic mesoderm promotes neuronal differentiation in part by downregulating Fgf8. Here we identify retinoic acid (RA) as this somitic signal and show that retinoid and FGF pathways have opposing actions. FGF is a general repressor of differentiation, including ventral neural patterning, while RA attenuates Fgf8 in neuroepithelium and paraxial mesoderm, where it controls somite boundary position. RA is further required for neuronal differentiation and expression of key ventral neural patterning genes. Our data demonstrate that FGF and RA pathways are mutually inhibitory and suggest that their opposing actions provide a global mechanism that controls differentiation during axis extension.
脊椎动物身体轴的延伸涉及从尾侧干细胞区衍生的新细胞的逐步产生及随后的分化；然而，维持尾侧祖细胞并协调分化的分子机制仍知之甚少。成纤维细胞生长因子（FGF）维持尾侧祖细胞，其减弱对于神经元和中胚层分化以及确定体节边界的位置是必需的。此外，体节中胚层部分地通过下调Fgf8来促进神经元分化。在这里，我们确定视黄酸（RA）为这种体节信号，并表明类视黄醇和FGF信号通路具有相反的作用。FGF是分化的一般抑制因子，包括腹侧神经模式形成，而RA在神经上皮和轴旁中胚层中减弱Fgf8，在那里它控制体节边界位置。RA对于神经元分化和关键腹侧神经模式形成基因的表达也是必需的。我们的数据表明FGF和RA信号通路相互抑制，并表明它们相反的作用提供了一种在轴延伸过程中控制分化的全局机制。
