The formation of gametes
and the first cell divisions of the fertilized egg in mammals are prone to
errors. Sometimes the wrong number of chromosomes is passed on to the
offspring, or the first division leads to two nuclei instead of one in the
two-cell embryo. In most cases, these errors result in miscarriages. Judith
Reichmann has shown what leads to these errors in mouse embryos.
FRANKFURT am MAIN. Today, Dr. Judith Reichmann is receiving the €60,000
Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers 2020. Dr.
Reichmann, who works at the European Molecular Biology Laboratory (EMBL) in
Heidelberg, researches the sources of chromosomal abnormalities in eggs and
embryos of mice and their potential contribution to miscarriages. Mice
synthesize a protein called Tex19.1, which maintains chromosome cohesion during
the formation of oocytes and protects sperm cells from genetic damage. Without
this protein, many mouse embryos have the wrong number of chromosomes and die
after a few cell divisions. Errors also occur when the fertilized egg splits
into two daughter cells. Reichmann was able to show that the paternal and
maternal chromosome sets are not passed on via one but two mitotic spindles. As
a result, the two sets of chromosomes sometimes drift apart during the cell
division process so that the two-cell embryo ends up with two haploid cell
nuclei instead of one diploid cell nucleus.
Reichmann discovered the dual spindle formation
using light-sheet microscopy, which she developed further for this purpose.
Mouse embryos do not tolerate continuous light exposure and therefore cannot be
examined with a conventional microscope in high spatiotemporal resolution. This
has precluded detailed live-imaging analyses in the past. In light-sheet microscopy, illumination occurs only in
the plane that is actually being observed, while other parts of the embryo
remain in the dark. "Judith Reichmann has shown how mice make sure that
their offspring have the correct number of chromosomes, and only one cell
nucleus. If this process fails, reproduction is compromised," the
Scientific Council´s statement reads. "Reichmann's research may one day
contribute to reducing the rate of miscarriages in women - provided that the
sources of error identified in mice also apply to human reproduction".
Reichmann discovered that the Tex19.1 protein
indirectly stabilizes the chromosomes during meiosis. This process ensures that
the gametes enter fertilization with a single set of chromosomes, for without
this process the number of chromosomes would double with each generation. In
oocytes, stabilization of the chromosomes is needed because meiosis is
interrupted for a long time and is only completed upon fertilization. When
Tex19.1 is missing, the chromosomes drift apart in the egg. As a result, many
embryos among the offspring do not inherit the correct number of chromosomes.
Reichmann's discovery of the dual spindles during
the first cell division of the fertilized egg has toppled a textbook statement.
Up to now, it had been assumed that the parental chromosomes merge in the
fertilized egg and are distributed to the two daughter cells via a single
spindle apparatus. Reichmann was able to show that the paternal and maternal
chromosomes are grouped separately from each other in two spindles and are then
distributed to the poles. Even in the nucleus of the two-cell embryo, maternal
and paternal chromosomes initially remain in different hemispheres before they
finally mix during subsequent cell divisions.
If Reichmann´s findings in mice also hold for human
embryogenesis, and the human paternal and maternal chromosomes only merge in
the two-cell embryo as well, a central assumption of the German Embryo
Protection Act may have to be reconsidered. It states that human life begins
when maternal and paternal chromosomes join; by this definition, the two-cell
embryo rather than the zygote would take centre stage.
The Paul Ehrlich and Ludwig Darmstaedter Prize for
Young Researchers has been awarded since 2006 in recognition of outstanding achievements
in biomedical research.
Short
biography of Dr. Judith Reichmann
Judith
Reichmann (35) studied applied biology at the University of Applied Sciences
Bonn-Rhein-Sieg. At the end of her studies, she moved to the University of
Aberdeen in Scotland where she pursued a bachelor's degree in genetics. At the
University of Edinburgh, she completed her doctorate on the development of
oocyte and sperm cells. Reichmann came to EMBL as a postdoctoral fellow in 2012
to investigate cell division at the beginning of life using the latest
microscopy techniques. She has been working as a research scientist at EMBL
since 2017. Reichmann is married and has two children.
Paul Ehrlich and Ludwig
Darmstaedter Prize for Young Researchers
The Paul Ehrlich and Ludwig Darmstaedter Prize
for Young Researchers, awarded for the first time in 2006, is conferred once a
year by the Paul Ehrlich Foundation on a young investigator working in Germany
for his or her outstanding achievements in the field of biomedical research.
The prize money must be used for research purposes. University faculty members
and leading scientists at German research institutions are eligible for
nomination. The selection of the prizewinner is made by the Scientific Council
on a proposal by the eight-person selection committee.
The Paul Ehrlich Foundation
The
Paul Ehrlich Foundation is a legally dependent foundation which is managed in a
fiduciary capacity by the Association of Friends and Sponsors of the Goethe
University, Frankfurt. The Honorary Chairman of the Foundation, which was
established by Hedwig Ehrlich in 1929, is Professor Dr. Katja Becker, president
of the German Research Foundation, who also appoints the elected members of the
Scientific Council and the Board of Trustees. The Chairman of the Scientific
Council is Professor Thomas Boehm, Managing Director at the Max Planck
Institute of Immunobiology and Epigenetics in Freiburg, the Chair of the Board
of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and
Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor
Wilhelm Bender, in his function as Chair of the Association of Friends and
Sponsors of the Goethe University, is Member of the Scientific Council. The
President of the Goethe University is at the same time a member of the Board of
Trustees.
Further
information
You can obtain selected
publications, the list of publications and a photograph of the prizewinner from
Dr. Hildegard Kaulen, phone: +49 (0) 6122/52718, e-mail:
h.k@kaulen-wissenschaft.de and at www.paul-ehrlich-stiftung.de.