Biomedical subjects

Michael Kessel

Publications and source records attributed to Michael Kessel.

7 recordsLinked to original sources

PubMed2004

Primordial germ cell migration in the chick and mouse embryo: the role of the chemokine SDF-1/CXCL12.

As in many other animals, the primordial germ cells (PGCs) in avian and reptile embryos are specified in positions distinct from the positions where they differentiate into sperm and egg. Unlike in other organism however, in these embryos, the PGCs use the vascular system as a vehicle to transport them to the region of the gonad where they exit the blood vessels and reach their target. To determine the molecular mechanisms governing PGC migration in these species, we have investigated the role of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) in guiding the cells towards their target in the chick embryo. We show that sdf-1 mRNA is expressed in locations where PGCs are found and towards which they migrate at the time they leave the blood vessels. Ectopically expressed chicken SDF-1alpha led to accumulation of PGCs at those positions. This analysis, as well as analysis of gene expression and PGC behavior in the mouse embryo, suggest that in both organisms, SDF-1 functions during the second phase of PGC migration, and not at earlier phases. These findings suggest that SDF-1 is required for the PGCs to execute the final migration steps as they transmigrate through the blood vessel endothelium of the chick or the gut epithelium of the mouse.

Amino Acid Sequence↗

PubMed2004

Geminin coordinates cell cycle and developmental control.

Growth and differentiation are two major themes in embryonic development. Numerous cell divisions have to be regulated on the path from a unicellular embryo, the zygote, to the multicellular structures of a mature being. Numerous functions, specializations and cellular identities have to be generated, in order to form a complex and mature animal. Numerous mechanisms have to control the correct assignment and acquisition of cellular fates, as well as the right timing and allocation of cells. Therefore, a strict coordination has to occur between embryonic patterning and the cell cycle. From this point of view, dual roles or mutual interactions of typical proliferation and developmental control genes are likely. Recently, new light was shed on these issues by identifying the nuclear protein Geminin as a molecular coordinator between the cell cycle and axial patterning. We summarize the role of Geminin in cell cycle, in the embryonic patterning controlled by Hox genes, providing insights into cell cycle regulators in embryonic development, and conversely, typical developmental control genes in cell cycle regulation.

Animals↗

PubMed2004

Involvement of Pax6 and Otx2 in the forebrain-specific regulation of the vertebrate homeobox gene ANF/Hesx1.

During early vertebrate development, ANF homeobox genes are expressed in the prospective forebrain. Their regulation is essential for correct morphogenesis and function of the prosencephalon. We identified a 1-kb fragment upstream of the chicken GANF gene sufficient to drive lacZ expression in the endogenous expression domain. Concordant with the high conservation of this sequence in five investigated species, this element is also active in the corresponding expression domain of the zebrafish orthologue. In vivo analysis of two in vitro-identified Otx2 binding sites in this conserved sequence revealed their necessity for activation of the chicken ANF promoter. In addition, we identified a Pax6-binding site close to the transcriptional start site that is occupied in vivo by Pax6 protein. Pax6 and GANF exhibit mutually exclusive expression domains in the anterior embryonic region. Overexpression of Pax6 in chick embryos inhibited the endogenous GANF expression, and in Pax6(-/-) mice the expression domain of the murine ANF orthologue Hesx1 was expanded and sustained, indicating inhibitory effects of Pax6 on GANF. However, a mutation of the Pax6 site did not abolish reporter activity from an electroporated vector. We conclude that Otx2 and Pax6 are key molecules involved in conserved mechanisms of ANF gene regulation.

Amino Acid Sequence↗

PubMed2004

The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions.

Embryonic development is tightly controlled. The clustered genes of the Hox family of homeobox proteins play an important part in regulating this development and also proliferation. They specify embryonic structures along the body axis, and are associated with normal and malignant cell growth. The cell-cycle regulator geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. Here, we show that murine geminin associates transiently with members of the Hox-repressing polycomb complex, with the chromatin of Hox regulatory DNA elements and with Hox proteins. Gain- and loss-of-function experiments in the chick neural tube demonstrate that geminin modulates the anterior boundary of Hoxb9 transcription, which suggests a polycomb-like activity for geminin. The interaction between geminin and Hox proteins prevents Hox proteins from binding to DNA, inhibits Hox-dependent transcriptional activation of reporter and endogenous downstream target genes, and displaces Cdt1 from its complex with geminin. By establishing competitive regulation, geminin functions as a coordinator of developmental and proliferative control.

Amino Acid Sequence↗

PubMed2004

Highly restricted BMP10 expression in the trabeculating myocardium of the chick embryo.

Bone morphogenetic proteins (BMPs) control the development of diverse tissues during embryogenesis. Here, we report the expression of the BMP10 gene during chick development. BMP10 transcription is confined to the myocardium of atriae and ventricles in the forming heart from day 2 of development onwards (stage HH13). It correlates with the thickening of the innermost layer of the walls, i.e. the formation of myocardial ridges or trabeculae.

Animals↗

PubMed2004

The acquisition of neural fate in the chick.

Neural development in the chick embryo is now understood in great detail on a cellular and a molecular level. It begins already before gastrulation, when a separation of neural and epidermal cell fates occurs under the control of FGF and BMP/Wnt signalling, respectively. This early specification becomes further refined around the tip of the primitive streak, until finally the anterior-posterior level of the neuroectoderm becomes established through progressive caudalization. In this review we focus on processes in the chick embryo and put classical and more recent molecular data into a coherent scenario.

Animals↗

PubMed2004

Restricted expression domains of Ezrin in developing epithelia of the chick.

Ezrin is a member of the ERM- (Ezrin-Radixin-Moesin-) family of actin binding proteins, which function as linkers of the cortical cytoskeleton to components of the plasma membrane. Additional roles for Ezrin in intracellular signalling and ion channel regulation were suggested. We found Ezrin mRNA in the anterior endo- and mesoderm of chick gastrula stage embryos. In these tissues Ezrin message is strongly expressed throughout early development of the foregut (pharynx) and heart tube. During later stages of development, highly restricted expression domains of Ezrin mRNA were detected in the endodermal lining of the pharyngeal pouches, the mesonephric duct and tubuli, and in the ectodermal placodes giving rise to the inner ear, eye lens and olfactory epithelium.

Animals↗