收斂延伸是胚胎形狀變化的一個重要機(jī)制,,它涉及細(xì)胞的有序運動,導(dǎo)致它們的空間重排和整個組織沿著其中線的延伸,。一項新的研究表明,,在脊椎動物中,收斂延伸的方向是與身體軸向一致的,。一個以前人們不知道的,、內(nèi)在的前-后極性(其基礎(chǔ)是由Activin一樣的信號因子構(gòu)成的一個梯度),,將收斂延伸和中胚層形狀的形成聯(lián)系了起來,。封面所示為,在一個由實驗誘導(dǎo)的中胚層“外植體”中青蛙胚胎的細(xì)胞重排,。除胚胎外,,傷口愈合等與醫(yī)學(xué)有關(guān)的過程也涉及由細(xì)胞重排驅(qū)動的形態(tài)發(fā)生,對此,,收斂延伸是一個流行的實驗?zāi)P汀?/p>
Nature 430, 364 - 367 (15 July 2004); doi:10.1038/nature02620
Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning
Remodelling its shape, or morphogenesis, is a fundamental property of living tissue. It underlies much of embryonic development and numerous pathologies. Convergent extension (CE) of the axial mesoderm of vertebrates is an intensively studied model for morphogenetic processes that rely on cell rearrangement. It involves the intercalation of polarized cells perpendicular to the antero-posterior (AP) axis, which narrows and lengthens the tissue1, 2. Several genes have been identified that regulate cell behaviour underlying CE in zebrafish and Xenopus. Many of these are homologues of genes that control epithelial planar cell polarity in Drosophila1-5. However, elongation of axial mesoderm must be also coordinated with the pattern of AP tissue specification to generate a normal larval morphology. At present, the long-range control that orients CE with respect to embryonic axes is not understood. Here we show that the chordamesoderm of Xenopus possesses an intrinsic AP polarity that is necessary for CE, functions in parallel to Wnt/planar cell polarity signalling, and determines the direction of tissue elongation. The mechanism that establishes AP polarity involves graded activin-like signalling and directly links mesoderm AP patterning to CE.
Figure 1 AP polarity and chordamesoderm explant elongation. a–d, Mixed explants at the neurula (a, b) and tailbud (c, d) stage, viewed externally (a, c) and in sections (b, d). Prospective posterior chordamesoderm cells (animal one-third of dorsal lip) are green, anterior cells (middle one-third of lip) are red. e–g, Combined explants at the neurula stage. Shown are combinations of two anterior (e), two posterior (f), and one anterior and one posterior (g) aggregates. h, i, Section in situ hybridization of a stage-12 gastrula, dorsal side (h), and a stage-15 Keller sandwich (i) explant, showing expression of Xbra (left images) and chd (right images) in the chordamesoderm. Anterior is to the top; arrowheads indicate the blastopore. j, k, Combined explants after 1 h (j) and at the neurula stage (k). Cell lineage in j and k is the same as in b and d, respectively, with expression of chd (j, right) and Xbra (k, right) visualized by section in situ hybridization. Explants are initially flat from centrifugation (j), round up, and then elongate (k). See footnotes to Table 1 for abbreviations. Scale bars, 200 µm.
Figure 2 Activin-induced elongation. a, Explant preparation. b–e, Sections of tailbud stage explants stained with MZ15 antibody, showing vacuolated notochord cells in graded (b), uniform (c), combined (d) and mixed (e) explants. f–m, Morphology of graded (f), uniform (g), combined (h–l) and mixed (m) explants at the neurula stage. Each of the two aggregates combined was either induced identically (h–j) or differently (k, l). n–q, In situ hybridization of explant sections. n, o, Expression of Xbra (left images) and chd (right images) in graded (n) and uniform (o) explants at the neurula stage. The dotted lines (n) indicate the connecting part between anterior (upper) and posterior (lower) portions outside the plane of section. p, q, Expression of chd in combined explants after 1 h (p) and at the neurula stage (q). The discrete expression boundary (p) corresponds to lineage boundary (not shown). See footnotes to Table 1 for abbreviations. Scale bars, 200 µm.
Figure 3 Convergent extension and Wnt/PCP signalling. a, b, Cell intercalation 1 h after combining aggregates (a), and at stage 25 (b). Aggregates were either non-labelled or labelled with fluorescein dextran amine (FDA; green), rhodamine dextran amine (RDA; red) and Cascade Blue dextran amine (CBDA; blue). Arrows in b indicate intercalating cells. c, d, Graded explants injected with -galactosidase (-gal) mRNA (c) or PDZ (d) mRNA. e–h, Combined explants injected with -gal (e) or PDZ (f) mRNA, and Xbra expression in -gal- (g) and PDZ-injected (h) explants. i–l, PDZ is expressed in one of the two combined aggregates, whereas -gal is expressed in the other. Maximal constriction (white arrowheads) is in the -gal-expressing part, regardless of whether it received the lower (i) or higher (j) activin dose. k, l, RDA labelling (red) of a fifth of the cells in both parts shows that cells on the -gal side appear polarized and aligned (blue arrowheads), whereas cells on the PDZ side (green, PDZ–GFP) do not (purple arrowheads), regardless of whether the activin dose was higher (k) or lower (l) on the PDZ side. m, n, Xdsh–GFP localization in untreated (m) and activin-treated (n) uniform explants. Left, Xdsh–GFP; middle, 8C8 antibody against integrin, demarcating cell membranes; right, overlay of Xdsh (green) and 8C8 (red) signal. See footnotes to Table 1 for abbreviations. Scale bars, 200 µm, except for those in panels l and n (50 µm).