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ScienceWeek
DEVELOPMENTAL BIOLOGY: ON EMBRYONIC AXES IN THE MOUSE
The following points are made by P.P Tam (Current Biology 2004 14:R239):
1) Conventional wisdom about the determination of the embryonic axes in the mouse is long on speculation and short on understanding of the cellular and molecular mechanisms. Two analyses of the orientation of the embryonic axis during the remodeling of the pre-gastrula mouse embryo[1,2] have recently provided a more complete description of the intricate developmental processes at work. The findings show that while the prospective anterior-posterior embryonic axis is consistently aligned with the transverse axis of the uterus, it is not always oriented along the long axis of the pre-gastrula embryo, as would be predicted from the anatomy of the gastrulating embryo. Rather, the anterior-posterior axis is first oriented along the shorter transverse axis of the embryo and then it switches to alignment with the longer axis following the remodeling of the pre-gastrula embryo.
2) A major milestone in embryonic development is the generation of the architectural asymmetry that delineates the orientation and polarity of the three axes -- anterior-posterior, dorso-ventral and left-right -- of the basic body plan. The mouse embryo goes through the first four days of development like other eutherian pre-implantation embryos, dividing up the fertilized egg into multiple blastomeres and putting the descendants of the blastomeres into a blastocyst. The blastocyst is a vesicular structure containing an outer epithelial layer of trophectoderm enclosing a fluid-filled cavity. A cluster of cells, the inner cell mass which gives rise to the embryo proper, is attached to the internal wall on one side of the vesicle. This lopsided location of the inner cell mass gives the mouse embryo a distinct asymmetry. The side of blastocyst on which the inner cell mass is localized becomes the embryonic pole and the diametrically opposite side is the abembryonic pole; these poles define an embryonic-abembryonic axis.
3) Superimposed on this visible morphological asymmetry is a more subtle breach of radial symmetry. When viewed from the embryonic pole, the inner cell mass does not form a perfectly round shape, but acquires an oblong one with a short and a long diameter; the latter defines an axis of bilateral symmetry that is orthogonal to the embryonic-abembryonic axis. The longer axis, however, is unique in that one end of it is marked by the presence of the second polar body and/or the tilting of the inner cell mass away from the embryonic-abembryonic axis[3-5].
4) The second polar body, which is extruded by the oocyte as it completes meiosis shortly before fertilization, is a landmark of the animal pole of the zygote; the opposite side, by default, is the vegetal pole. The animal-vegetal axis, in conjunction with the point of sperm entry, not only defines the orientation of the first cleavage of the zygote but also seems to influence the differential allocation of the progeny of the first two blastomeres to cells in the embryonic versus abembryonic compartment of the blastocyst [3]. These observations raise the intriguing possibility that the pertinent morphogenetic program for defining cell fates and patterning the mouse embryo is installed very early in development.
References (abridged):
1. Mesnard, D., Filipe, M., Belo, J.A., and Zernicka-Goetz, M. (2004). Emergence of the anterior-posterior axis after implantation relates to the re-orienting symmetry of the mouse embryo rather than the uterine axis. Curr. Biol. 14, 184-196
2. Perea-Gomez, A., Camus, A., Moreau, A., Grieve, K., Moneron, G., Dubois, A., Cibert, C., and Collignon, J. (2004). Initiation of gastrulation in the mouse embryo is preceded by an apparent shift in the orientation of the anterior-posterior axis. Curr. Biol. 14, 197-207
3. Gardner, R.L., Meredith, M.R., and Altman, D.G. (1992). Is the anterior-posterior axis of the fetus specified before implantation in the mouse?. J. Exp. Zool. 264, 437-443
4. Gardner, R.L. (1997). The early blastocyst is bilaterally symmetrical and its axis of symmetry is aligned with the animal-vegetal axis of the zygote in the mouse. Development 124, 289-301
5. Smith, L.J. (1980). Embryonic axis orientation in the mouse and its correlation with blastocyst relationships to the uterus. Part 1. Relationships between 82 hours and 4 1/4 days. J. Embryol. Exp. Morphol. 55, 257-277
Current Biology http://www.current-biology.com
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ROLE OF SPERM IN MAMMALIAN EMBRYONIC PATTERNING
In many animal species, the point of entry of a sperm into an egg cell during fertilization apparently determines the orientation of the division of the one-celled embryo into two cells. The entry point also apparently determines the orientation of one of the 3 embryonic "axes", which form later in development and which mark the 3 dimensions of the embryo: front to back, head to tail, and left to right. Until now, this determining effect of the sperm entry point was believed not to be true for mammals.
The following points are made by K. Piotrowska and M. Zernicka-Goetz (Nature 25 Jan 01 409:517):
1) The authors point out that despite a lack of known determinants of cell fate in the mouse embryo, the spatial patterning of the embryo is evident early in development. The vertical axis of the embryo after transplantation in the uterus can be traced back to organization of the pre-implantation *blastocyst, and this in turn reflects the organization of the *cleavage stage embryo and the *animal-vegetal axis of the *zygote. These findings suggest that the cleavage pattern of normal development may be involved in specifying the future embryonic axis, but how and when this pattern becomes established is unclear. In many animal eggs, the sperm entry position provides a cue for embryonic patterning, but until now no such role has been found in mammals.
2) The authors report that in the mouse sperm entry position predicts the plane of initial cleavage of the mouse egg cell and can define embryonic and *abembryonic halves of the future blastocyst. In addition, the embryonic cell inheriting the sperm entry position acquires a division advantage and tends to cleave ahead of its sister. Since cell identity reflects the timing of the early cleavages, these events together shape the blastocyst, the organization of which will become translated into axial patterning after uterine implantation.
3) The authors conclude that 2 axes of the blastocyst become specified in the single-cell embryo. One of these axes is defined by the animal pole, and the second axis, the embryonic-abembryonic axis, relates to the sperm entry point. These axes are initially not fixed and can be re-established if development is perturbed. The authors suggest that the direction of blastocyst organization by the plane of cleavage and cellular identity by the order of cleavage may offer an interpretation of the regulative events that occur following perturbation of development. In normal development, the orientation and timing of cleavage are mechanisms that progress together, but one might act as a failsafe mechanism for the other when development is perturbed. The authors conclude: "It will be a future challenge to determine how these axes are initiated by the earliest events of embryogenesis and how they become transformed into the final body pattern.
In a commentary on this work, Roger A. Pedersen (Nature 25 Jan 01 409:473) states: "This finding represents a leap forward in our knowledge of how the mammalian embryo acquires its body pattern. It also suggests that mammals might share other features of axis formation with species such as frogs, for which we have a better understanding of the effects of fertilization on embryonic organization."
Nature http://www.nature.com/nature
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Notes by ScienceWeek:
cleavage: The term "cleavage" refers to a series of consecutive cell divisions, with the cells produced during cleavage called "blastomeres". During cleavage, almost no growth occurs between consecutive divisions, and the total volume of the embryo does not substantially change: the size of the cells is reduced by almost half at each division. At the beginning of cleavage, cell divisions tend to occur synchronously in all blastomeres, and the number of cells is doubled at each division. As cleavage progresses, this synchrony of division is lost. In most animals, cleavage follows an orderly pattern, with the first division in the plane of the main axis of the egg cell. This cleavage plane is arbitrarily called "vertical". The second cleavage plane is again vertical but at right angles to the first, producing 4 equal cells arranged around the main axis of the egg. The third cleavage plane is at right angles to both the first and second cleavage planes and is horizontal (or equatorial). Subsequent divisions may alternate between vertical and horizontal cleavage planes, but ultimately cleavage divisions become randomly oriented. The above cleavage pattern is typical of many animal groups, but variations are common in many species. Although the shape and volume of the embryo do not change during cleavage, an important change in gross organization occurs: as the blastomeres are produced, they move outward, leaving a centrally-located fluid-filled cavity, and the embryo at this stage approximates a hollow ball and is known as a "blastula". The formation of the blastula marks the end of the cleavage stage of embryonic development.
blastocyst: The "morula" is an early embryonic *cleavage stage consisting of a solid mass of cells (blastomeres). The next stage is the "blastula" stage, in which the cells form a hollow sphere. The "blastocyst" is an early form of the blastula stage, an egg in the later stages of cleavage. The blastocyst consists of a hollow fluid-filled ball of cells and an inner cell mass (embryonic stem cells) from which the embryo develops.
animal-vegetal axis: After fertilization, the egg cell acquires polarity, two poles of the egg becoming distinct from each other. At one pole, known as the "animal pole", the cytoplasm is apparently more active and contains the nucleus. At the other pole, called the "vegetal pole", the cytoplasm is apparently less active and contains most of the nutritive material ("yolk") of the egg. The general organization of the future animal is apparently closely related to the polarity of the egg. (The archaic and confusing terminology "animal" vs. "vegetal" in this context derives from 19th century microscopy, but is still in use.)
zygote: In general, the term "zygote" refers to the cell formed by the union of male and female gametes (sperm and egg cells).
abembryonic [region]: In general, the area of the mammalian blastocyst opposite the region where the embryo is formed (opposite the stem cell region).
ScienceWeek http://scienceweek.com
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