Research

Our workgroup is interested in the function and differentiation of red blood cells (RBCs) of the chicken embryo. Due to the key function of the RBCs for oxygen supply, interferences of the embryonic /fetal erythropoiesis are a fundamental cause of a defect or abortive development.
The first population of the embryonic RBCs performs all steps of the terminal differentiation within the bloodstream and it allows access to normal erythroid progenitor cells which in adult organisms are normally found in the bone marrow. For this reason, the blood of the chicken embryo is an easy-accessible model to study aspects of embryonic/fetal RBC function and erythroid differentiation of vertebrates.

Main projects

Regulation of the erythroid Pyrimidine- and Purine nucleotide pools during embryonic development

ATP as well UTP and CTP are the main allosteric effectors of the embryonic hemoglobins. Via in vivo hypoxia/hyperoxia, characteristic changes of the nucleotide pattern occur which result in the modification of the O2 transport function of the RBCs.We investigate the underlying cellular and biochemical mechanisms and the control by hormones.
(contact persons: Baumann, Dragon)

cAMP-dependent transcriptional control in embryonic red blood cells

The stimulation of mid-to late-stage embryonic RBCs by ß-adrenergic or adenosine A2a receptor agonists and the subsequent activation of the adenylyl cyclase lead to accumulation of the important erythroid enzymes carbonic anhydrase II and pyrimidine nucleotidase I. The induction is the consequence of activated gene expression and is accompanied by the synthesis of other regulatory proteins which are known to accompany differentiation processes of many cell types (epithelial, neuronal and myogenic): We identified 1.) c-Fos, a transcription factor, 2.) TOB (=APRO6), a protein with anti-proliferative properties, and 3.) IFR1 (=PC4=TIS7=IFRD1), a protein with supports differentiation by an unknown mechanism. We want to unravel the cellular function of the three proteins in the context of the terminal differentiating RBCs to better understand the process and regulation of terminal erythroid maturation.
(Contact person: Dragon)

The relevance of embryonic RBCs for metabolisation and as source of extra-cellular nucleotides

The activation of receptors for purine- and pyrimidine nucleotides generally depends on the metabolisation of the nucleotides (ATP, UTP) that are released by cells. During this process, embryonic RBCs play a key role: they are a source for extra-cellular ATP/UTP/cAMP and due to their high 5'-ectonucleotidase activity, they are able to rapidly hydrolyse extra-cellular nucleotides. We investigate the developmental profile, as well as the regulation of the erythroid 5'-ectonucleotidase activity.
(Contact person: Baumann)


Methods

Techniques used for chick embryo and mice:

Biochemical and molecular techniques: