Formation of the body axes in the early mammalian embryo
Mechanisms of axis formation and mesoderm induction during the gastrulation period of embryonic development are at the centre of this project. Using the rabbit as the main model organism and its anterior marginal crescent (AMC) in the pre-primtive-streak embryonic disc as a landmark (Fig. A, Viebahn et al. 1995), we intend (1) to describe functional relationships between transcription factors (such as brachyury, goosecoid, ANF) and growth factors (BMPs, nodal, activin, etc.) during mesoderm formation (Fig. B), (2) to establish a concise fate map in the late pre-streak stages of the mammalian embryonic disc (cf. Viebahn et al. 2002), and (3) define signals responsible for a head organizer property resident in the AMC (cf. Knoetgen et al. (1999). The results are compared to those of other vertebrate classes (birds, amphibia, fish) to reveal possible evolutionary relationships which might give clues as to other mechanisms acting, for example, as safeguards in mammalian development. Interdisciplinary relationships exist with the pathology of malignant tumours (epithelio-mesenchymal transformation) and with malformations of the body axes (Siamese twins, left-right asymmetries). This project is funded by the DFG priority programme 1027 "Evolution of developmental processes".
Differentiation of germ cells (germ line)
Differentiation of germ cells during embryonic development is under investigation
using the mitochondrium-associated epitope PG2 which is defined by a monoclonal
antibody (Viebahn et al. 1998). This epitope is specifically expressed
in germ cells of the rabbit from their earliest appearance as primordial
germ cells (PGC) during gastrulation. Initially, the epitope is expressed
- similar to the transcription factor Oct4 - in all cells of the embryo
(Fig.) and has thus, together with its exclusive expression in primordial
and adult germ cells, the characteristics of a germ line marker. This
project aims at (1) cloning the PG2 epitope, (2) determining time point
and mode of the establishment of the germ cell lineage in mammalian embryos
other than the mouse, and (3) at isolating permanent embryonic germ cell
lines for targeted mutagenesis in the rabbit. This research is funded
by the DFG Priority Program 1109 'Embryonic and Somatic Stem Cells - Regenerative
Systems for Cell and Tissue Repair' and by the DAAD to support a cooperation
with INRA, France.
In an attempt to provide a legal basis for assisted reproduction techniques in humans, the German law for the protection of human embryos (Embryonenschutzgesetz) defined in 1991 the unification of the pronuclei (syngamy) as the time point from which human embryonic life is to be protected from experimental or other research. However, depending on the scientific progress or even religious or political ideas, other time points of development may be declared to be criticial with regard to the protection of developing human life as well: (1) penetration of the oocyte by the spermium; (2) first transcription from the newly assembled embryonic nuclear DNA at the 2- to 4-cell stage; (3) start (on day 6 of development) or completion (day 14) of implantation as the beginning of intrauterine development typical for mammals; (4) the appearance of the primitive streak (on day 14) establishing the basis for the development of separate individuals or (5) formation of the neural tube (neurulation, week 4) as the hallmark of the high cognitive development of the human race. Our department aims at monitoring the coverage of biological and ethical questions relating to early human development and to assisted reproductive techniques in the media and tries to support the discussion with material that explains the biomedical facts.
Viebahn, C. (2002) Eine Skizze der embryonalen Frühentwicklung des