Marlow Florence, Gonzalez Encina M, Yin Chunyue, Rojo Concepcion, Solnica-Krezel Lilianna
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
Development. 2004 Jan;131(1):203-16. doi: 10.1242/dev.00915. Epub 2003 Dec 3.
The vertebrate posterior body is formed by a combination of the gastrulation movements that shape the head and anterior trunk and posterior specific cell behaviors. Here, we investigated whether genes that regulate cell movements during gastrulation [no tail (ntl)/brachyury, knypek (kny) and pipetail (ppt)/wnt5] interact to regulate posterior body morphogenesis. Both kny;ntl and ppt;ntl double mutant embryos exhibit synergistic trunk and tail shortening by early segmentation. Gene expression analysis in the compound mutants indicates that anteroposterior germ-layer patterning is largely normal and that the tail elongation defects are not due to failure to specify or maintain posterior tissues. Moreover, ntl interacts with ppt and kny to synergistically regulate the posterior expression of the gene encoding bone morphogenetic protein 4 (bmp4) but not of other known T-box genes, fibroblast growth factor genes or caudal genes. Examination of mitotic and apoptotic cells indicates that impaired tail elongation is not simply due to decreased cell proliferation or increased cell death. Cell tracing in ppt;ntl and kny;ntl mutants demonstrates that the ventral derived posterior tailbud progenitors move into the tailbud. However, gastrulation-like convergence and extension movements and cell movements within the posterior tailbud are impaired. Furthermore, subduction movements of cells into the mesendoderm are reduced in kny;ntl and ppt;ntl mutants. We propose that Ntl and the non-canonical Wnt pathway components Ppt and Kny function in parallel, partially redundant pathways to regulate posterior body development. Our work initiates the genetic dissection of posterior body morphogenesis and links genes to specific tail-forming movements. Moreover, we provide genetic evidence for the notion that tail development entails a continuation of mechanisms regulating gastrulation together with mechanisms unique to the posterior body.
脊椎动物的后体由塑造头部和前躯干的原肠胚形成运动以及后体特异性细胞行为共同构成。在此,我们研究了在原肠胚形成过程中调节细胞运动的基因[无尾(ntl)/短尾,克尼派克(kny)和细尾(ppt)/Wnt5]是否相互作用以调节后体形态发生。kny;ntl和ppt;ntl双突变胚胎在早期体节形成时均表现出协同的躯干和尾巴缩短。复合突变体中的基因表达分析表明,前后胚层模式基本正常,尾巴伸长缺陷并非由于未能指定或维持后体组织。此外,ntl与ppt和kny相互作用,协同调节编码骨形态发生蛋白4(bmp4)的基因的后部表达,但不调节其他已知的T盒基因、成纤维细胞生长因子基因或尾侧基因。对有丝分裂和凋亡细胞的检查表明,尾巴伸长受损并非仅仅由于细胞增殖减少或细胞死亡增加。在ppt;ntl和kny;ntl突变体中的细胞追踪表明,腹侧来源的后尾芽祖细胞移入尾芽。然而,类似原肠胚形成的汇聚延伸运动和后尾芽内的细胞运动受损。此外,在kny;ntl和ppt;ntl突变体中,细胞向内胚层的内陷运动减少。我们提出,Ntl和非经典Wnt信号通路成分Ppt和Kny在平行的、部分冗余的信号通路中发挥作用,以调节后体发育。我们的工作开启了后体形态发生的遗传学剖析,并将基因与特定的尾巴形成运动联系起来。此外,我们为尾巴发育需要调节原肠胚形成的机制与后体特有的机制共同作用这一观点提供了遗传学证据。