Prof. Dr. Thomas Holstein
Prof. Dr. Thomas Holstein
Im Neuenheimer Feld 230
Fon +49 6221 54-5679
Fax +49 6221 54-5678
thomas.holstein AET cos.uni-heidelberg.de
Regeneration, stem cells, and pattern formation at the base of metazoan evolution
Our model organisms are the freshwater polyp Hydra and the starlet sea anemone Nematostella, two genetic model organisms and members of the >550 Million year old phylum Cnidaria. Hydra is famous for its unlimited regenerative capacity that is based on its stem cells, and Nematostella offers unique mechanistic insights into early development and neurogenesis. Both models help us to understand basic molecular mechanisms in stem cell biology, the evolution of the central nervous system, and of developmental mechanisms. Of further interest are nematocytes, a sophisticated neuronal cell type that synthesize the nematocyst, an organelle with outstanding biophysical properties.
Wnt and TGF-β signaling. The molecular nature of signaling centers (organizers) plays a pivotal role in the origin and evolution of metazoan body. The families of Wnt/Wingless secreted proteins act as short-range inducers and long-range organizers in axis formation, organogenesis and tumor formation in vertebrates. In cnidarians, the canonical Wnt signaling pathway is expressed in the polyp’s oral signaling center (organizer), which corresponds to the blastopore of metazoan embryos. Along the body axis Wnts control axial and neuronal differentiation (“wnt-code”). We analyze the gene regulatory network of Wnt genes by using transgenic lines and promotor constructs for genes encoding members of the Wnt and TGF-β signal pathways as well as by testing corresponding recombinant Hydra and Nematostella proteins.
Stem cell recruitment in Hydra pattern formation. We study the mechanisms mediating the self-renewal capacity of Hydra stem cells and the recruitment of stem cells during pattern formation processes in steady state animals and during regeneration. Our overall objective is to understand the regulatory network controlling stem cell recruitment and differentiation. To this end we have developed and established a number of experimental approaches that will facilitate a comprehensive analysis of stem renewal and differentiation in a whole organism.
The evolutionary origin of the central nervous system. The cnidarian nerve net is diffuse and no brain-like structures have been reported. The goal of our work is to uncover the molecular mechanism of neurogenesis in cnidarians and to understand how it is related to the origin, evolution and patterning of neurogenesis among the metazoans. We analyze the properties and the behavior of pro-neuronal cells in Hydra and Nematostella by confocal laser scanning microscopy (CLSM) and 2-photon microscopy.
Proteome and evolution of nematocytes. Nematocysts are the most conspicuous character of cnidarians. Their explosive discharge is one of the fastest events in biology and the forces sustained during discharge require extraordinary mechanical strength and elastic modulus in the capsular material. We identified the protein map of the nematocyst and now analyze the assembly process (antibodies and GFP-fusion proteins) and evolutionary origin of these organelles.
(i) Systematic approaches to identify the key transcription factors in the Wnt regulatory network of the Hydra Organizer.
(ii) Unravel the regulatory logic of Hydra stem cells during maintenance and differentiation including epigenetic signatures involved signaling pathway regulation.
(iii) Proteomic and genetic approaches to understand the initiation of regeneration.
(iv) Neurogenesis in Hydra and Nematostella and the evolutionary origin of nematocytes.