Essner J J, Johnson R G, Hackett P B
Department of Genetics and Cell Biology, University of Minnesota, St. Paul 55108-1095, USA.
Differentiation. 1999 Jul;65(1):1-11. doi: 10.1046/j.1432-0436.1999.6510001.x.
Nuclear receptors play key roles in anterior/posterior (A/P) axis formation during vertebrate embryogenesis. Within this gene family, retinoic acid receptors and retinoic acid itself have profound influences on the establishment of the A/P axis. Thyroid hormone receptors are expressed during early periods of development, long before the establishment of the thyroid gland, and are able to interact with retinoic acid receptors. Here we examined the ability of the thyroid hormone receptor alpha 1 to affect early embryonic development by mRNA injection of either repressor or activator forms of the thyroid hormone receptor. Overexpression of either the thyroid hormone receptor alpha 1 or a constitutive repressor form, v-erbA, caused a swelling in the rostral hindbrain. These defects were associated with disorganization and loss of rhombomere borders as well as an increase in the number of acetylcholine esterase positive cells. This phenotype correlated with a reduction in hoxa1 expression during gastrulation. Furthermore, injection of either thyroid hormone receptor alpha 1 or v-erbA mRNA repressed a reporter gene that contained a retinoic acid response element, demonstrating the ability of the thyroid hormone receptor alpha 1 to repress retinoic acid signaling during gastrulation. In contrast, embryos treated with retinoic acid alone or embryos injected with thyroid hormone receptor alpha 1 and treated with the thyroid hormone analog TRIAC displayed a similar set of defects, including loss of the midbrain-hindbrain border and severe disruption of the rostral hindbrain. These studies support the involvement of retinoic acid and its receptors in the direct control of Hox gene expression and the early patterning of the zebrafish central nervous system.
核受体在脊椎动物胚胎发育过程中的前后轴形成中发挥关键作用。在这个基因家族中，视黄酸受体和视黄酸本身对前后轴的建立有深远影响。甲状腺激素受体在发育早期表达，远在甲状腺形成之前，并且能够与视黄酸受体相互作用。在这里，我们通过注射甲状腺激素受体的阻遏物或激活剂形式的mRNA，研究了甲状腺激素受体α1影响早期胚胎发育的能力。甲状腺激素受体α1或组成型阻遏物形式v-erbA的过表达导致吻侧后脑肿胀。这些缺陷与菱脑节边界的紊乱和丧失以及乙酰胆碱酯酶阳性细胞数量的增加有关。这种表型与原肠胚形成期间hoxa1表达的减少相关。此外，注射甲状腺激素受体α1或v-erbA mRNA会抑制一个含有视黄酸反应元件的报告基因，这表明甲状腺激素受体α1在原肠胚形成期间能够抑制视黄酸信号传导。相比之下，单独用视黄酸处理的胚胎或注射甲状腺激素受体α1并同时用甲状腺激素类似物TRIAC处理的胚胎表现出一组相似的缺陷，包括中脑-后脑边界的丧失和吻侧后脑的严重破坏。这些研究支持视黄酸及其受体参与直接控制Hox基因表达以及斑马鱼中枢神经系统的早期模式形成。
