Developmental and Stem Cell Biology MajorLecturers

The development of a living organism from a single cell is a spectacular process.  It represents a masterpiece of temporal and spatial coordination of gene expression, of cellular events and communication between many different cell and tissue types.

Aim of  research and teaching in the Major „Developmental and Stem Cell Biology“  is to gain understanding of the mechanisms that guide a fertilized egg and the resulting daughter cells through cell divisions and complex morphogenetic rearrangements, with crucial checkpoints in time and space to ultimately emerge the body axes as well as complex structures such as eyes, brain or flowers. The structures of the adult organism need not only to be established, but are also maintained throughout adult life by the activity of stem cells in their respective niches.

Organismal development and the role of stem cell mediated growth and homeostasis is in the research focus of the scientists participating in the Major „Developmental and Stem Cell Biology“.

Ingrid Lohmann – Major director

Current research in my lab is based on an integrated approach of advanced genomic, genetic, molecular, and biochemical methods together with extensive computational analysis and simulation to determine on the one hand how Hox proteins orchestrate different aspects of development, with a special focus on stem cell maintenance in the testis as well as neurogenesis and motor control. On the other hand, we are interested in elucidating how Hox transcription factors achieve the spatio-temporally restricted expression of their target genes in specific cell and tissue types. And finally, we study processes involved in cancer formation and progression, in particular how metabolic changes due to mitochondrial dysfunction multiply the output of signaling pathways critically controlling proliferation.

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Ingrid Lohmann

Sergio P. Acebron

The development of a living organism from a single cell is a spectacular process.  It represents a masterpiece of temporal and spatial coordination of gene expression, of cellular events and communication between many different cell and tissue types.

Aim of  research and teaching in the Major „Developmental and Stem Cell Biology“  is to gain understanding of the mechanisms that guide a fertilized egg and the resulting daughter cells through cell divisions and complex morphogenetic rearrangements, with crucial checkpoints in time and space to ultimately emerge the body axes as well as complex structures such as eyes, brain or flowers. The structures of the adult organism need not only to be established, but are also maintained throughout adult life by the activity of stem cells in their respective niches.

Organismal development and the role of stem cell mediated growth and homeostasis is in the research focus of the scientists participating in the Major „Developmental and Stem Cell Biology“.

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Sergio Acebron

Alexander Aulehla

Timing of Mammalian Embryogenesis

During an embryo's journey from a single cell to a complex organism, countless patterning processes unfold with remarkable precision, spatially but also in respect to temporal sequence, or timing. This temporal aspect of embryonic development is the focus of our research. How is time measured during embryonic development and what extrinsic and intrinsic signals control this timing? How are embryonic oscillators/clocks employed during patterning? What are the dynamics of signalling pathways?

To approach these questions, novel methodologies are required. We are generating novel real-time reporter mouse lines using knock-in technology that enables visualisation and quantification of temporal dynamics at different levels in the context of mouse embryonic development. Using in vivo imaging, we are focusing on the somite segmentation clock, an oscillatory system that is thought to control the formation of the pre-vertebrae that form periodically in a head-to tail sequence within the paraxial mesoderm. In mouse embryos this clock, with a periodicity of around two hours, drives oscillatory activity of several signalling pathways (Wnt, Notch and Fgf signalling) in the developing mesoderm.

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A. Aulehla

Michael Boutros

Signaling and Functional Genomics

Our group is interested in cellular signaling transduction and its role in development and disease. Inappropriate control of signaling has been linked to many diseases and is frequently associated with cancer. We study principle mechanisms of signal transduction by genetic and genomic approaches using Drosophila as a model system as well as cell-based approaches. One particular interest in the lab is in the regulation and mechanism of Wnt signaling pathways.

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M. Boutros

Lazaro Centanin

Developmental Biology/Physiology

My lab is interested in stem cells and how they behave in their natural environment. We use fish as model organisms, since they contain stem cells that permanently contribute to the growth of every organ and during the entire life. We have developed colorful genetic tools based on the CRE / LoxP system that allow us to follow stem cells and their progeny over time. Using these tools we address the potential and the mitotic activity of stem cells during homeostasic growth, and how these change during regeneration.

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Lazaro Centanin

Nicholas Foulkes

Circadian Clock Biology

Almost every aspect of plant and animal biology shows day - night rhythms. Many persist even under constant conditions however with period lengths that are not precisely 24 hours and for this reason they are termed “circadian” (Circa-diem). Central to the generation of circadian rhythms is an endogenous circadian clock which is constantly reset ("entrained") by environmental factors such as light to ensure that it remains synchronised with the natural 24 hour cycle.

Classically, the circadian clock in vertebrates was shown to reside in so-called central “oscillator” or “pacemaker” structures. In mammals the suprachiasmatic nucleus (SCN) of the hypothalamus and the retina are both the sites of pacemakers while in lower vertebrates, the pineal gland also appears to contain an additional pacemaker. Within these structures, individual cells have been shown to contain clocks which are synchronised in the context of the tissue. In mammals, the SCN clock is entrained by light via photoreceptors in the retina which appear to be distinct from the rod and cone ocular photoreceptor cells. However, more recently this centralized model for the vertebrate clock has been challenged by the discovery of clock functions in diverse tissues and cell types.

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N. Foulkes

Thomas Greb

Growth and Cell Fate Regulation

How are cellular properties coordinated during growth and development to generate functional organs and whole bodies? In our lab we use lateral growth of plant shoots as an example to address this fundamental question. Lateral growth is based on the tissue-forming properties of a group of stem cells called the cambium, the activity of which leads to the production of secondary vascular tissue (wood and bast). Considering its function as a stem cell niche that is essential for the constant production of new tissues in a highly differentiated cellular environment, the cambium represents an ideal model for addressing questions concerning the regulation of cell identity and how growth processes are aligned with endogenous and exogenous requirements.

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Thomas Greb

Annika Guse

Molecular Basis of Coral Symbiosis

Coral reefs are the world's most diverse marine ecosystems and their existence depends upon a functional symbiosis between dinoflagellates (genus Symbiodinium) and their coral host. A range of environmental stressors including elevated seawater temperature, acidification, and pollution causes the obligate symbiosis between corals and their intracellular algae to break down. The long-term goal of the Guse Lab is to dissect the molecular mechanisms underlying the establishment and maintenance of coral symbiosis. For our research, we are using the emerging model organism Aiptasia (a small marine sea anemone) in combination with classical approaches as well state-of-or the art molecular and cell biology techniques and microscopy.

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Annika Guse

Thomas Holstein

Signaling Centers and the Evolution of Body Axes

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.

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Thomas Holstein

Steffen Lemke

Evolution of Fly Gastrulation

Morphogenesis sculpts simple, 2D epithelial sheets into complex, 3D structures. During animal development, morphogenesis can be first observed during gastrulation: set up by embryonic patterning, regulatory networks modulate cell junctions and the cytoskeleton to change cell-mechanical properties and direct the generation of shape. It is not known at which level these often hierarchical developmental regulatory networks tolerate genetic changes, and what type of changes eventually lead to the evolution of novel form and function. We study gastrulation in comparable, yet divergent fly species and use them as test tube system to recapitulate how genetic evolution has led to morphogenetic diversity.

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Steffen Lemke

Jan Lohmann

Stem Cell Biology

Work in the department of Stem Cell Biology is focused on the regulatory programs governing shoot meristem function and the control of stem cell number in the reference plant Arabidopsis thaliana. To this end we employ an integrated approach of advanced genetic, genomic, and molecular methods together with computational analysis to determine how hard-wired genetic circuits underlying stem cell control are orchestrated and integrated with environmental signals.

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Jan Lohmann

Felix Loosli

Medaka fish: A population genetic model system

We use medaka fish for the following projects:

1. Epithelial polarity in the developing CNS: how does epithelial polarity of retinal progenitor cells control proliferation and differentiation?

2. In a collaboration with Nick Foulkes/ITG-KIT we have identified closely related nocturnal and diurnal medaka species. These species produce fertile offspring in intercrosses allowing a genetic dissection of the cellular and molecular mechanisms that underlie the choice between nocturnal and diurnal behaviour.

3. We are establishing a panel of more than one hundred inbred lines from a polymorphic wild population for genetic association studies of quantitative trait loci (QTL) in collaboration with Jochen Wittbrodt/COS-HD.

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F. Loosli

Ana Martin Villalba

Stem Cells and Cancer

Adult stem cells are involved in tissue homeostasis, response to injury and tumor initiation. Our current and future research centers on understanding the molecular program involved in the control of stem cell quiescence/activation in the brain and pancreas during homeostasis and disease, as well as its modulation by the innate immune system. Our research intends to contribute to the identification of molecular mechanisms involved in stem cell biology and tumor initiation and/or progression.

Ana Martin Villalba

Alexis Maizel

Molecular Embryology

Work in my laboratory focuses on understanding how plant organs, in particular roots, are shaped. This morphogenesis results from the combined action of the plant genes controlling cell identity, the mechanical interactions between cells and tissues, and the physical environment in which development takes place. However, very little is known about the perception of environmental inputs and their impact on morphogenesis. Our focus is to understand how temperature and water availability alter this process. Our work is based on an integrated approach of cell biology, molecular genetics, advanced microscopy, and biochemical methods together with computational analysis to advance our physical and biological understanding of how biological shapes arise.

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Alexis Maizel

Suat Özbek

Biochemistry of the Extracellular Matrix and Wnt

Our research is focused on the evolution of extracellular matrix and signaling molecules. In particular, we are interested in the evolution of complex features, as of organelles. In our lab we are applying biochemical, microscopic and structural techniques as well as systems biology approaches using functional genomics and proteomics. Our model organism is the cnidarian Hydra, which represents one of the most basal metazoan animals and a sister group to the bilateria thus offering important implications for comparative evolutionary questions. A unique feature of cnidarians is the possession of a stinging organelle called "nematocyst", which has been one of the main subjects of our studies. Nematocyst represent a speciaized form of extracellular matrix and their complex protein composition and morphogenesis offer an intriguing field of research.

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Suat Özbek

Gislene Pereira

Control of cell division/Stem cell development/Centrosome Biology

Work is our lab is centred on microtubule-based processes that influence cell division and intracellular signaling. We use mammalian stem and differentiated cells as well as a simple model system (Saccharomyces cerevisiae) to investigate following questions:

1. How polarised cells (including various stem cells) coordinate cell cycle progression with spindle orientation.

2. How cell division is controlled by a “Hippo”-like signalling cascade on a molecular level and how this misregulation leads to aneuploidy and cancer.

3. How centrosomes give rise to the primary cilium. The primary cilium is a microbutule-based organelle involved in signalling (e.g. Wnt and Shh) and thereby essential during embryonic development and for adult tissue homeostasis.

Methods used in our laboratory are yeast genetics, microscopy (live cell imaging, fluorescence and super-resolution microscopy, electron microscopy, FRAP, FRET), mammalian cell cultures in 2D and 3D (organoids), genome editing (CRISPR/Cas9), among others.

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Gislene Pereira

Gudrun Rappold

Developmental Disorders

The focus of our research interest is on the molecular elucidation of human disease with a special focus on growth and neuronal disorders. To uncover the basic mechanisms on the causes of these disorders, our work employs different cell culture and animal models (mouse, chicken, zebrafish) as well as differentiated stem cells. We would like to understand how mutations correlate with disease, how genes are regulated and how they contribute to differentiation and development. We work on three major topics:

  1. Limb development/Short stature/Homeobox genes: SHOX and targets
  2. Heart development/Pacemaker, Arrhythmia/Transcrption factors: SHOX2 and targets
  3. Brain development/Intellectual disability, Autism: FOXP1, SHANK2, SHANK3

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G. Rappold

Michael Raissig

Development of the plant epidermis

Plants use sunlight to turn carbon dioxide and water into the sugars we eat and the oxygen we breathe. Land plants form microscopic “breathing” pores on their leaves, the so-called stomata, to balance carbon dioxide uptake with water vapour loss. The grass family that includes the three major food crops rice, maize and wheat, form particularly efficient stomata; Grasses add lateral “helper cells” or subsidiary cells to the central guard cells, which makes the four-celled grass stomata faster to open and close and thus more water-efficient. We study how subsidiary cells are formed and how they functionally support guard cells using genetics and gene editing, (time-lapse) confocal microscopy and methods to measure actual gas exchange between the plant and the atmosphere.

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Michael Raissig

Uwe Strähle

Eye Development, Growth and Regeneration

The main focus of our laboratory is to elucidate the molecular mechanisms how organs such as the skeletal musculature and the central nervous system are built during embryogenesis and how they are maintained in a functional state in the adult animal using the zebrafish as model vertebrate. To this end, we identify key regulatory genes and decipher the underlying gene regulatory networks. We use genetic techniques and imaging to understand the molecular and cellular mechanisms that control for example the proliferation of neural stem cells in the embryo and adult. Or to understand how injured nervous tissue or muscle cells are repaired.

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Strähle

Joachim Wittbrodt

Molecular Neurobiology

The lab is studying neuronal cell proliferation and differentiation in the developing, growing and regenerating eye and brain of fish (zebrafish, medaka) as model system. We are combining genetic, molecular and cell biological approaches with advanced imaging approaches to decipher the basic mechanisms that govern the balance of cell proliferation and differentiation in vivo.  Novel tools developed in the lab allow to perform clonal analysis in 4D by the induction of the expression of genes of interest at physiological levels in individual retinal cells of any cell type. The combination of these approaches with the systematic analysis of transcription factors that control the expression of key genes will contribute to a functional understanding of the molecular processes that govern the proliferation and differentiation of retinal stem cells.

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Joachim Wittbrodt

Detlev Arendt

 Evolution of Gastrulation and Central Nervous Systems in Bilateria

The Arendt group looks to understand the origin and evolution of the central nervous system (CNS) by studying simple marine model organisms. Our aim is to gain a systems view of the annelid  Platynereis dumerilii brain and nervous system and to track the evolutionary history of all constituent cell types by identifying and investigating their evolutionary counterparts in the sea anemone Nematostella and the amphioxus. This will involve investigations of cell type-specific gene regulatory networks in all species as well as neurobiological and behavioural approaches.

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Detlev Arendt

Alfonso Martinez Arias

Structure and Function of Living Matters

We are interested in the structure and function of Living Matter with a special focus on the processes that generate tissues and organs from single cells through interactions between protein and gene regulatory networks. Cells use these networks to create and read programmes of gene expression and use these to interact with each other and differentiate into the multiple cell types that configure the building blocks of an organism. Our research is focused on how the activity of molecular networks is transformed into tissues for organ building. We address this problem through a combination of classical genetics, quantitative cell biology, image analysis and modelling.

We use mouse Embryonic Stem (ES) cells and Drosophila Intestinal Stem Cells (ISC) to ask questions about: Stochastic and deterministic processes in cell fate decisions; Cell and tissue dynamics during morphogenesis; Wnt/Notch signalling in developmental homeostasis.

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Arias

Carmen Ruiz de Almodovar

Neuro-vascular communication during development of the central nervous system

My research group is interested in understanding neuro-vascular communication during development of the central nervous system.  The two main questions that we try to answer are (1) how do “traditional” angiogenic molecules also affect directly neurodevelopment and (2) how do neurons and blood vessels communicate during the development of the central nervous system. For this, we use a combination of mouse genetics, organotypic cultures, cell biology, biochemistry and molecular biology approaches.

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Carmen Ruiz de Almodovar

Aurelio Teleman

Molecular Genetics and Molecular Toxicology of Vertebrate Nervous System and Muscle Development

During both normal animal development and tumorgenesis, cells need to grow and to divide. Regulation of cell division (i.e. the cell cycle) has been extensively studied. In comparison, the mechanisms regulating cell growth (i.e. the accumulation of cell mass) are less well understood. The Teleman lab studies cell growth and its regulation. To grow, cells need to produce nucleotides, amino acids and lipids. Consequently, understanding cell growth requires understanding metabolism. Cells decide to grow, however, based on the presence of nutrients and growth factors. This information is processed via signaling pathways such as the insulin pathway. Therefore, understanding cell growth also requires understanding signaling pathways. Since these mechanisms are conserved amongst animals, the Teleman lab studies these pathways using a combination of human tissue culture and the genetically tractable fruit fly Drosophila.

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Aurelio Teleman

Andreas Trumpp

Signal Transduction in Cancer and Metabolism

Over the last 15 years the Trumpp team has contributed to a better understanding of the molecular and cellular basis of normal and malignant stem cell self-renewal and differentiation. For example, they have shown that the most potent hematopoietic stem cells (HSC) are in a state of deep dormancy during homeostasis and that stress signals (chemotherapy) or bacterial/viral infections cannot only activate these HSCs to produce new stem cells and progenitors, but make them also exquisitely sensitive to chemotherapy induced killing. In addition to a MDS and leukemic stem cell program, the team has also identified circulating metastasis stem cells in the blood of breast cancer patients, which offer novel possibilities for the design of better diagnostic and therapeutic tools for metastatic breast cancer. Prof. Trumpp is also scientific editor at the “Journal of Experimental Medicine”, founding member and 2013/2014 President of the “German Stem Cell Network” (GCSN) as well as member of numerous international scientific advisory and review boards.

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A Trumpp