Mammals: Plan of the body determined only after fertilization

Eggs of mice have no "North Pole"

Mouse zygote in the phase before the first furrow © Max Planck Institute for Immunobiology
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The later form of the embryo is not yet defined in the ova of mammals. The level of the first cell division develops independently of morphological structures. Rather, it is determined by the random location of the two pronuclei of egg and sperm cell. This has been proven by scientists from the Freiburg Max Planck Institute of Immunobiology.

Unlike most other animals, the body axes, such as the front and back, head and tail, right and left, in the mammals are not yet fixed in the egg. However, recent studies have suggested that certain morphological characteristics of the mammalian egg cell may dictate the future embryonic axis. However, a detailed study using time-lapse imaging at the Max Planck Institute for Immunobiology in Freiburg has shown that the level of the first cell division develops independently of morphological structures in the egg cell. Rather, it is determined by the random location of the two pronuclei of egg and sperm cell. So, mammalian cells do not seem to have markers that affect the shape of the later embryo - an important finding given over one million babies born to date through artificial insemination.

Polarity in the preimplantation embryo

Does the seemingly homogeneous mammalian egg cell have anything that would allow it to predict the three-dimensional attachment of the later embryo, as is possible in most other species? The emergence of polarity in the mammalian preimplantation embryo has long been a controversial issue among scientists. However, the predetermination of the human ovum is central to the recent advances in reproductive medicine: Worldwide, more than one million ART (Assisted Reproductive Technology) infants have emerged, with an increasing number being due to direct injection of sperm into the egg a mostly random site within the human oocyte is generated by ICSI (intracytoplasmic sperm injection).

Developmental biologists have previously assumed that mammals are the only creatures lacking preformed orientation signals in the fertilized egg. However, recent studies have shown that the embryonic-embryonic (Em-Ab) axis of the mouse blastocyst is perpendicular to the first cleavage plane. The second polar body (2pb), the remnant of the second meiotic division in the oocyte, was used as a stationary marker of the ovarian animal's polar (A-pole) and assumed that the first cleavage plane was always meridional (north-south) and coincident with the assumed animal-vegetal (AV) axis of the egg. Therefore, it was thought that the polarity of the mouse embryo is already established in the egg, as with most other species.

First furrow separated from the ovum AV axis

Scientists at the Max Planck Institute of Immunobiology in Freiburg have now followed the development of numerous M use embryos from the egg cell to the two-cell stage under a specially developed admission procedure, so to speak, in a "time-lapse" approach. Surprisingly, they found that in about half of the embryos, the first ridge occurs separately from the ovum AV axis, and the second pole of the ridge approaches before and after the rupture, This indicates that, in contrast to previous assumptions, the second pole body does not mark a stationary "north pole" (A-pole) for the embryo, and that therefore - in the absence of a stable morphological reference point, which could define the AV axis - the thesis of a predefined AV axis in the egg cell of mammals must be rejected. display

But what determines the first division level in the mammalian cell? Is it a completely coincidental process? The Freiburg scientists observed that in the mouse, a few hours after fertilization, two pronuclei (pronuclei) are formed, each with the female chromosomes or the male chromosomes in the periphery of the egg cell. During the following 20 hours, these pronuclei move toward the center of the egg cell and finally face each other without fusing. Then the mitosis, ie the actual core division, takes place. Their detailed analysis showed that the first furrow plane always coincides with the plane separating the two opposite pronuclei in the center of the egg cell.

Microtubule networks

Immunofluorescence staining for the cytoskeleton indicates that microtubule networks play an important role in the development of this process: the cell must bring two parental chromosomes into their centers before they can evenly divided into two daughter cells. The experimental investigations showed that the first cleavage plane is not determined in the early interphase, but rather determined by the newly formed topology of the two pronuclei.

For their investigations, the researchers had developed a special recording technique (time-lapse imaging), with which the development in the egg cell can be tracked dynamically. This made it obvious that the egg cell of the mouse has no predeterminate polarity. Still unanswered is the question of when and how the polarity develops in the mammalian embryo. The researchers want to investigate this question next.

The scientists report on their findings in the latest issue of the science magazine Nature.

(idw - MPG, 19.07.2004 - DLO)