Meiosis: divide and multiply
Fascinated by questions surrounding egg formation, fertilization and the early stages of embryo development, Edouard Van Beneden discovered the process of what would later be called meiosis in 1883.
Différents moments de la pénétration du spermatozoïde et début de la formation du fuseau du centre.
When 1+1=3 or more, the law of nature thumbs its nose at mathematics. Over the course of evolution, the species that inhabit our planet have invented various ways of achieving this. For many of them, it all begins with fertilization. A spermatozoon enters an ovum, and the nuclei fuse to form the first cell of the new individual in the making. The processes involved in the production of male and female gametes, the fusion of their nuclei and the development of the embryo are well known today. But this has not always been the case. Not so long ago, in the early 19th century, scientists had no idea how a female egg oroocyte undertook the transformations that lead to the development of a living being. " In the mid-19th century, there was an explosion of knowledge in the field of cytology, the study of the cell. It was then that Theodor Schwann developed cell theory ," explains Vincent Geenen, Professor of Embryology at the University of Liège. " And this was to influence many fields, including embryology, i.e. the development of individuals from a single egg in all animal species ". At the time, Karl Ernst von Baer, a German-Baltic biologist, described the development of the embryo from three layers: the endoderm, the mesoderm and the ectoderm. The cells making up each layer have different, specific purposes. For his part, German biologist and committed Darwinist Ernst Haeckel noted that all animal species pass through a common stage: the gastrula. " Haeckel says that, at this stage, you can't distinguish one species from another, even though their eggs are basically very different sizes and the adult individuals have very distinct morphologies", continues Vincent Geenen.
Contact or penetration fertilization?
Edouard Van Beneden (1846-1910), the son of a palaeontologist and a keen natural scientist, shone in the scientific arena from the very start. Particularly interested in oocyte maturation, fertilization and the first stages of embryonic development, he immersed himself in these questions from the very start of his scientific career, at the age of 20. He used the rabbit as a model animal and made his observations under the microscope. " At that time, the rabbit was the most common animal used for experiments; it was the model in vogue, just like Drosophila or zebrafish are today ", explains the Professor of Embryology. At the age of 24, while lecturing in zoology and comparative anatomy at ULg, Edouard Van Beneden wrote his first manuscript based on his observations. It was published in 1875 (1). " In this manuscript, he confines himself to observations and refuses to engage in any reflection," emphasizes Vincent Geenen. Among other things, he describes how there are two nuclei in the oocyte before it begins to transform. These are two pronuclei. " The only hypothesis that Edouard Van Beneden puts forward in this manuscript is that these two pronuclei present in the oocyte could fuse, but he does not demonstrate this ," continues the scientist. " It was Oscar Hertwig who demonstrated this later, in 1876, based on observations of sea urchin eggs ". What used to be known as fertilization is based on the "contact theory". Scientists believe that it is contact between a spermatozoon and an egg that leads to the first stages of embryo development, without the spermatozoon penetrating the egg. In the same 1875 manuscript, Edouard Van Beneden also reports that, after contact between sperm and egg, the egg settles in the uterus and begins what he calls its "fragmentation". " Today we talk about segmentation ," explains Vincent Geenen. " It describes how the egg gives rise to two daughter cells, then four, etc." Still in this segmentation stage, Edouard Van Beneden also mentions the appearance of a blastopore, a structure fundamental to the establishment of the three leaflets that make up the embryo. All these observations were made by this "Mozart of science" with the help of microscopy and staining techniques that are now in full expansion.
Reduce genetic material by half
Edouard Van Beneden became Professor at the 4université de Liège at the age of 28! After using the rabbit as a model animal, he turned to the Ascaris(Ascaris megalocephala) , a parasitic horse worm. " His father worked a lot on intestinal worms, and Edouard Van Beneden had noticed that Ascaris has very large spermatozoa," explains Vincent Geenen. " He probably thought that this would enable him to settle the question of whether or not spermatozoa penetrate oocytes ". In 1883, the researcher published a book of over 470 pages (2), bringing together the results of his research in three areas: egg maturation, fertilization and the first stages of segmentation. Among his discoveries, this time he demonstrates the penetration of the spermatozoon into the oocyte, and points out that the male pronucleus is located in the center of the oocyte, while the oocyte's pronucleus is on the periphery. " However, he goes on to say that these two pronuclei never merge ...". But it was his work on ovogenesis that caught the attention of the scientific world. " Thanks to the staining of what he calls the "chromatic rings ", he shows that the oocyte eliminates polar globules containing the same genetic material as that found in the female pronucleus ", says Vincent Geenen. " He therefore hypothesizes that these polar globules enable the genetic material contained in the oocyte to be halved. He thus laid the foundations for knowledge of the meiosis process, which was given its name in 1905 . His drawings are so precise that we can clearly see the most elaborate description of what would become meiosis, i.e. the division of sex cells. It was he who first put forward the idea of halving genetic material through a process that is very clearly different from classical mitosis. Although today we call chromosomes chromatic loops, we've kept the term polar globule, introduced at the time by Edouard Van Beneden.
First observations of the centrosome
This process of ovogenesis, during which polar globules are formed to halve the genetic material, is one of the most important phenomena in egg formation. " This process can also be observed in the plant world ," adds Vincent Geenen. In the course of his observations, Edouard Van Beneden made another discovery: " He talks about little dots that appear and thinks they play an important role in egg division ". These little dots are what Theodor Boveri, a German biologist, described and called the centrosome in 1888, the organizing center of the cell's microtubules.
Edouard Van Beneden's contribution to knowledge in the field of biology is immense, and difficult to summarize both in terms of its scope and the links between his work and other major scientific figures of the time. He made ULg a leading university in the field of embryology, particularly comparative embryology, and left a legacy in the form of a school of zoology and embryology. "Today, as human embryology is mainly a descriptive science, it has given way to developmental biology using molecular biology techniques ," says Vincent Geenen. " We work with other models, such as the zebrafish, which is the most advanced model animal for molecular and genetic analyses in this field ". Edouard Van Beneden's work received numerous awards throughout his career (see box). The eminent scientist died at the age of 74, in 1910, on his cot in his office at the Institute of Zoology. Like a captain aboard his ship, he stayed the course through the centuries.
Scientific references
(1) « Egg maturation, fertilization and early embryonic development in mammals, based on research in rabbits ", Bulletins de l'Académie Royale des Sciences de Belgique. Vol. 40, p. 646, 1875 ».
Consult the publication on ORBi
(2) « Research into egg maturation, fertilization and cell division." Ghent, Leipzig & Paris, Librairie Clemm & G. Masson, 1883.
Consult the publication on ORBi
See Edouard Van Beneden's biography
Consult Édouard Van Beneden's scientific publications
Vincent Geenen is Director of Research at the F.R.S.-FNRS in Belgium, Professor of Embryology and History of Biomedical Research at the University of Liège, and Head of the Endocrinology Clinic at Liège University Hospital. Since January 2012, he has headed the Immunoendocrinology Center at the GIGA-Rresearch institute. He is secretary of the Fonds Léon Fredericq for biomedical research at the CHU de Liège and a member of the SVS-4 commission of the F.R.S.-FNRS.
For almost 30 years, Vincent Geenen and his team have been working on the thymus, the central lymphoid organ of the immune system. His research has shown that the thymus plays a unique role in educating the immune system to recognize and tolerate neuroendocrine functions, and that thymus dysfunction is involved in the development of selective autoimmunity in type 1 diabetes. Currently, the Immunoendocrinology Center is developing a new type of negative/tolerogenic vaccination against type 1 diabetes.
Vincent Geenen was also coordinator of the FP6 integrated project Eurothymaide (2004-2008). This consortium of 20 academic laboratories and 5 SME biotech companies worked to develop new diagnostic and therapeutic approaches to autoimmune diseases, based on new insights into the natural tolerogenic mechanisms of the thymus.
Consult the list of Vincent Geenen's publications
For a better understanding
Gamete: male (spermatozoid) or female (ovum) sex cell that enables sexual reproduction.
Ovocytes: female cells present in the ovaries of women from before birth. Only a small number can be fertilized between puberty and the menopause. These mature oocytes, destined to be fertilized by spermatozoa, are called ova (although the term is not scientific).
Gastrula : embryo resulting from gastrulation, during which the three constituent layers (ectoderm, mesoderm, endoderm) are formed in the correct order.
Pronucleus: cellular structure corresponding to each of the two nuclei, one from the spermatozoid, the other from the ovum, which are the two gametes, male and female, enabling the creation of the fertilized egg, evolving (normally) into the embryo, the fetus and finally the newborn.
Blastopore: During animal embryogenesis, when the vegetative pole of the coeloblastula invaginates during gastrulation, an opening is created: the blastopore. This gives access to the archenteric cavity located in the invaginated sac, the outline of the digestive tract. The destiny of the blastopore allows us to identify two major cuts in bilaterally symmetrical animals. In the first series, the blastopore of the gastrula becomes the mouth of the adult; it never takes part in the formation of the anus, which is built later. This character defines the protostomians (annelids, molluscs, etc.). In a second group, the blastopore of the gastrula gives rise to the anus or marks its place; the mouth corresponds to a neo-formation. This character defines the deuterostomians (echinoderms, stomocordates, pogonophores, tunicates, cephalocordates, vertebrates).
Microtubules: fibers making up the cell's cytoskeleton.
Centrosome: microtubule-organizing cell center.
Polar globule : two or three small cells formed during oocyte meiosis.
