A forkhead gene related to HNF-3beta is required for gastrulation and axis formation in the ascidian embryo.
A forkhead gene related to HNF-3beta is required for gastrulation and axis formation in the ascidian embryo.
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发表时间：
1997-09
期刊：
影响因子：
4.6
通讯作者：
C. L. Olsen;William R. Jeffery
中科院分区：
文献类型：
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作者：
C. L. Olsen;William R. Jeffery
我们在海鞘中分离出HNF-3/叉头基因家族的一个成员，以确定翼螺旋基因在脊索动物发育中的作用。MocuFH1基因是从Molgula culata cDNA文库中分离出来的，其叉头dna结合结构域与斑马鱼轴向和啮齿动物hnf -3 β最相似。MocuFH1是一个单拷贝基因，但在m.o ocata基因组中至少有一个其他相关的叉头基因。MocuFH1基因在卵裂后期开始的内胚层、间质和脊索细胞中表达。在原肠胚形成过程中，MocuFH1的表达发生在植物极内陷的内胚层细胞中，以及在胚孔前唇和外侧唇上内陷的脊髓和间质细胞中。然而，这种基因在胚孔后唇上的肌细胞中不表达。MocuFH1在相同的细胞系中继续表达，在神经形成和轴形成期间，然而，在尾芽期，MocuFH1也在脑和脊髓的腹侧细胞中表达。利用反义寡脱氧核苷酸（ODNs）研究了MocuFH1基因的功能作用，该基因在原肠胚形成过程中瞬间降低MocuFH1转录水平。经反义odn处理的胚胎正常分裂并开始原肠胚形成。然而，原肠胚形成不完全，一些内胚层和脊索细胞不能进入胚胎并进行后续运动，轴形成异常。相比之下，不表达MocuFH1的前瞻性肌肉细胞会经历内化，然后表达肌肉肌动蛋白和乙酰胆碱酯酶，这是肌肉细胞分化的标志。结果表明，MocuFH1在原肠胚形成和轴形成过程中是内胚层和脊索前体细胞形态发生运动所必需的。抑制MocuFH1表达对海鞘胚胎轴形成的影响与小鼠中HNF-3 β敲除突变的影响相似，这表明HNF-3/叉头基因在脊索动物的身体计划组织中具有古老而基础的作用。
We have isolated a member of the HNF-3/forkhead gene family in ascidians as a means to determine the role of winged-helix genes in chordate development. The MocuFH1 gene, isolated from a Molgula oculata cDNA library, exhibits a forkhead DNA-binding domain most similar to zebrafish axial and rodent HNF-3beta. MocuFH1 is a single copy gene but there is at least one other related forkhead gene in the M. oculata genome. The MocuFH1 gene is expressed in the presumptive endoderm, mesenchyme and notochord cells beginning during the late cleavage stages. During gastrulation, MocuFH1 expression occurs in the prospective endoderm cells, which invaginate at the vegetal pole, and in the presumptive notochord and mesenchyme cells, which involute over the anterior and lateral lips of the blastopore, respectively. However, this gene is not expressed in the presumptive muscle cells, which involute over the posterior lip of the blastopore. MocuFH1 expression continues in the same cell lineages during neurulation and axis formation, however, during the tailbud stage, MocuFH1 is also expressed in ventral cells of the brain and spinal cord. The functional role of the MocuFH1 gene was studied using antisense oligodeoxynucleotides (ODNs), which transiently reduce MocuFH1 transcript levels during gastrulation. Embryos treated with antisense ODNs cleave normally and initiate gastrulation. However, gastrulation is incomplete, some of the endoderm and notochord cells do not enter the embryo and undergo subsequent movements, and axis formation is abnormal. In contrast, the prospective muscle cells, which do not express MocuFH1, undergo involution and later express muscle actin and acetylcholinesterase, markers of muscle cell differentiation. The results suggest that MocuFH1 is required for morphogenetic movements of the endoderm and notochord precursor cells during gastrulation and axis formation. The effects of inhibiting MocuFH1 expression on embryonic axis formation in ascidians are similar to those reported for knockout mutations of HNF-3beta in the mouse, suggesting that HNF-3/forkhead genes have an ancient and fundamental role in organizing the body plan in chordates.