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First published online March 9, 2006
doi: 10.1242/10.1242/dev.02304

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Patterning the early Xenopus embryo

Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.

View larger version (38K): [in a new window]   Fig. 1. Characteristics of Xenopus laevis early development. (A) The different cell cycles and the external appearance of (a) the fertilized egg, and (b) two-cell, (c) mid-blastula and (d) early gastrula stages. Aa and Ab are views from the animal pole, Ac from the side and Ad from the vegetal pole. (Aa) Cycle 1 is approximately 90 minutes in length and has G1 and G2 phases. The next 11 divisions have no gap phases and occur every 20-30 minutes. (Ac) At the mid-blastula stage, the embryo consists of 4000 cells, gap phases reappear, the cycle lengthens to 50 minutes and zygotic gene expression commences. This marks the mid blastula transition (MBT). (Ad) The following cell cycle is longer (90 minutes), and the 15th cycle marks entry into gastrulation, which is a period of mitotic quiescence. (B) The features of the (a) fertilized egg, (b) the mid-blastula and (c) early gastrula, which are all viewed in section from the side. (Ba) Sperm entry activates the microtubule polymerization, which drives the rotational movement of the outer shell of cytoplasm (cortical cytoplasm) away from the sperm entry point (black arrow). Maximal rotation away from the sperm entry point occurs at a point at the circumference that subtends a 30° angle from the vegetal pole (red arrow). A dye mark placed on this spot (where 14 cell cycles later the dorsal lip of the blastopore forms) marks the beginning of gastrulation (red arrow in Bc). Immediately above the dorsal lip is the region of the Spemann Organizer (shown as a blue trapezoid in Ad). (Bb) At the mid-blastula stage, the embryo is described as having three regions, the animal cap, equatorial or marginal zone and vegetal mass, explants of which are dissected along the broken black lines shown.

View larger version (31K): [in a new window]   Fig. 2. The relationship of the embryonic dorsal axis to the definitive dorsal axis. (A) The cell movements of gastrulation obliterate the blastocoel, enclose a new cavity (the archenteron) and move cells into new positions. A patch of cells (red) in the region of the prechordal mesoderm lie above the dorsal lip of the blastopore at stage 10.25 (early gastrula stage). These cells move animalwards during gastrulation, away from the site of the blastopore lip, along the blastocoel roof to become part of the anterior (head) mesoderm by the end of gastrulation (stage 12). Meanwhile, the convergence extension of the chordamesoderm encloses the vegetal mass, and by the end of gastrulation, the definitive dorsoventral axis can be defined by a line at right-angles to the definitive anteroposterior axis. The obliterating blastocoel (black) lies on the ventral surface and the closing blastopore marks the definitive posterior end. (B) A comparison of the embryonic axes, at the early gastrula stage (stage 10.25), and the definitive axes, at the end of gastrulation (stage 12).

View larger version (26K): [in a new window]   Fig. 3. The endodermal regulatory network. VegT activates the transcription of pro-endodermal transcription factors, including Xsox17, GATA5 and Mixer, and of signaling molecules, including Xnr5, Wnt8 and the signaling antagonist cerberus. Vg1 and activin B also activate signaling pathways that lead to the transcription of the signaling antagonists chordin and cerberus, and the signaling molecule Xnr2. Xnr2, Xnr5 and Wnt8 are important mesoderm-inducing molecules, responsible for the transcriptional activation of pro-myogenic genes Xbra and eomesodermin, and FGF genes, which can regulate specific myogenic genes such as MyoD. Cerberus suppresses Xnr, Wnt and BMP signals extracellularly, and is required for head (prechordal) mesoderm formation, while BMP suppression by chordin is required for notochord formation. Signaling molecules are shown in blue and signaling antagonists in red.

View larger version (19K): [in a new window]   Fig. 4. The epidermal regulatory network. BMP signaling activates target genes directly, including Xvent2 and Msx1 (which activate the epidermal pathway and suppress neural fates when ectopically overexpressed). Xvent2 and Msx1 regulate the more-restricted pro-epidermal genes Xap2, Dlx3 and Xgrhl1, which can directly regulate epidermal structural genes such as the cytokeratin gene Xk81.1a, but which do not have neural-inhibiting functions.

View larger version (25K): [in a new window]   Fig. 5. The neural regulatory network. Animal cells are directed towards a neural fate beginning at the late blastula stage and continuing through gastrulation. Neural induction requires both suppression of the BMP-Smad1-Msx pathway by the BMP antagonists chordin, noggin and follistatin, and the activation of FGF signaling. Cells begin to express proneural genes (Sox2, SoxD) at the gastrula stage. By the end of gastrulation, the deeper layer of the pro-neural ectoderm activates specific neuronal precursor markers, including Xngnr1, which in turn regulates primary neuronal differentiation via XneuroD and N-tubulin. Primary neurogenesis requires the function of the maternal chromatin remodeling protein Brg1.

View larger version (14K): [in a new window]   Fig. 6. Cell movements at the dorsal lip of the blastopore during early gastrulation. During the first 2 hours of gastrulation, the vegetal mass undergoes an active inward surging (black arrow) in the animal direction, such that the animal part of the vegetal mass expands, increasing the area of the blastocoel floor, while the vegetal part contracts. This movement drives the first phase of involution of the prechordal mesoderm (red). After involution, prechordal mesoderm cells become actively migratory and migrate animally. Their movement is stopped by mid-gastrula stage by their firm adhesion to the substrate, the proneural animal cap cells. The chordamesoderm (purple) then undergoes convergence extension movements to cover the vegetal mass and close the blastopore. The bottle cells (black) indicate the site of dorsal lip formation.

View larger version (23K): [in a new window]   Fig. 7. The central role of Xbra in convergence extension and somite formation. FGF activates pathways through FGFR1 and Xbra, leading to convergence extension movements and myogenic specification. Xnr3 also activates FGFR-dependent Xbra expression, but only in the embryonic dorsal area. Xbra causes convergence extension movements by activating the expression of zygotic Wnt11. Wnt11 signaling causes convergence extension in a dishevelled-dependent manner that does not involve ß-catenin, the so-called `non-canonical Wnt pathway'. A separate pathway regulating convergence extension involves the activation of paraxial protocadherin downstream of Xlim1. The cytoplasmic kinase regulator genes sprouty and spred regulate whether cells undergo convergence extension or somite formation in response to FGFR stimulation (see text for details).

View larger version (21K): [in a new window]   Fig. 8. Signaling combinations that influence cell fate in the early Xenopus embryo. Mid-blastula cells are pluripotent, and many factors determine the fate of their progeny. Of major importance in regulating the expression of proneural, myogenic, endodermal and epidermal transcription factors, are the BMP, Xnr (+activin+Vg1), FGF and Wnt signaling pathways. As described in the text, loss-of-function experiments support the combinations of signals shown here as being crucial for ectodermal (neural and epidermis), mesodermal (head mesoderm, notochord, somite) and endodermal fates, at the late blastula and gastrula stages. The specification of blood islands, heart, intermediate and lateral plate mesoderm are not considered in this review. Arrowhead indicates required repression of the activity of the ligand.