A5058850160- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Zebrafish Biomedical Research Applications
- Genomics and Chromatin Dynamics
- Aquaculture disease management and microbiota
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Developmental Biology and Gene Regulation
- Invertebrate Immune Response Mechanisms
- Cancer-related gene regulation
- RNA Research and Splicing
- Reproductive System and Pregnancy
- Hair Growth and Disorders
- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
- RNA and protein synthesis mechanisms
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- Single-cell and spatial transcriptomics
- Fungal and yeast genetics research
- Aquaculture Nutrition and Growth
- Growth Hormone and Insulin-like Growth Factors
- TGF-β signaling in diseases
- Physiological and biochemical adaptations
Max Planck Institute of Immunobiology and Epigenetics
2014-2024
Institut des Maladies Génétiques Imagine
2019
Max Planck Society
2002-2014
DKFZ-ZMBH Alliance
1996-1997
German Cancer Research Center
1996-1997
University of Freiburg
1994-1995
Transgenic mice provide one of the best experimental systems to study gene function in vivo. Although transgenic carry additional genetic material every cell body, expression transgenes under control constitutive promoter/enhancer units, such as murine major histocompatibility complex promoter H2-Kb, CMV enhancer/promoter, Pgk-1 or chicken cytoplasmatic β-actin is often restricted a limited number tissues (1–5). However, for most dominant gain-of-function approaches addressing role given...
The transcription factor c-myb has emerged as one of the key regulators vertebrate hematopoiesis. In mice, it is dispensable for primitive stages blood cell development but essentially required definitive Using a conditional knock-out strategy, recent studies have indicated that self-renewal mouse hematopoietic stem cells. Here, we describe and characterize mutant in lower vertebrate, zebrafish Danio rerio . recessive loss-of-function allele ( t25127 ) was identified collection N -ethyl-...
Abstract Zebrafish has been advocated as an alternative animal model to study lymphocyte development, although the similarities in genetic requirements of lymphopoiesis between fish and mammals have not yet investigated. In this study, we examine role transcription factor Ikaros zebrafish lymphopoiesis. larvae homozygous for ikaros allele predicted lack C-terminal zinc fingers, T is absent; presence VHDμJμ rearrangements adolescent delayed mutants. mutant fish, cells expressing tcrb tcrd B...
In the mouse, product of nude locus, Whn, is required for keratinization hair shaft and differentiation epithelial progenitor cells in thymus. A bacterially expressed peptide representing presumptive DNA binding domain mouse whn gene vitro specifically binds to a 11-bp consensus sequence containing invariant tetranucleotide 5′-ACGC. transient transfection assays, such sites stimulated reporter expression about 30- 40-fold, when positioned upstream minimal promotor. Whn homologs from humans,...
Mutations in the whn gene are associated with phenotype of congenital athymia and hairlessness mouse rat. The encodes a presumptive transcription factor DNA binding domain forkhead/ winged-helix class. Two previously described null alleles encode truncated proteins lacking characteristic domain. In rat rnu allele here, nonsense mutation exon 8 was identified. whnrnu protein contains but lacks 175 C-terminal amino acids wild-type protein. To facilitate identification functionally important...
The epithelial thymic anlage develops from the third pharyngeal pouch. Pax9 is expressed in entire endoderm, and its function required for normal development of organs derived pouches. Here, we show that null mice, as an ectopic polyp-like structure larynx. It expresses Whn/Foxn1, a marker epithelium, but fails to perform caudo-ventral movement upper mediastinum. rudiment contains mesenchymal cells, blood vessels colonized by T cell progenitors. However, embryonic day 14.5 onwards, size...
Chemokines and chemokine receptors are key evolutionary innovations of vertebrates. They involved in morphogenetic processes play an important role the immune system. Based on analysis receptor gene family teleost genomes, expression patterns genes during embryogenesis wounding response young larvae Oryzias latipes , we identified cxcr3a as a marker innate cells. Cells expressing were characterized fish transgenic for cxcr3a:gfp reporter. In embryos larvae, -expressing cells motile healthy...
In mammals, the cytokine IL-7 is a key regulator of various aspects lymphocyte differentiation and homeostasis. Because difficulty identifying homologs in lower vertebrates paucity assay systems reagents, degree functional conservation signaling pathways, particularly those pertaining to development, unclear. this article, we report on analysis characterization three zebrafish mutants with severely impaired thymopoiesis. The identification affected genes by positional cloning revealed...
The molecular characteristics of the nude phenotype (alopecia and thymic aplasia) in humans rodents are unknown. locus encodes Whn, a transcription factor forkhead/winged-helix class. Expression Whn HeLa cells induced expression human hair keratin genes Ha3-II Hb5. Correspondingly, mice, which homozygous for loss-of-function mutation mouse mHa3 mHb5 is severely reduced. Characterization previously identified allele, nu(Y), revealed mis-sense (R320C) DNA binding domain Whn. This mutant...
Abstract Thymopoiesis strictly depends on proper differentiation of the thymic epithelial anlage. Differentiation cells (TECs) is controlled by Foxn1 transcription factor. The in vivo signals initiating and maintaining expression future thymus anlage are unknown. In mouse, bone morphogenetic protein (BMP) signaling required for maintenance TECs, as shown here lineage tracing using a Foxn1-driven Cre transgene. Loss after BMP inhibition reverts TECs to basal state pharyngeal epithelium unable...
Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members APOBEC3 branch are involved antiviral defense, whereas AID contributes to diversification antibody repertoires jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In extant jawless vertebrate, lamprey, two members implicated generation diversity variable lymphocyte receptors (VLRs). Expression studies linked CDA1 CDA2 genes assembly VLRA/C...
Abstract The stability of cellular phenotypes in developing organisms depends on error-free transmission epigenetic and genetic information during mitosis. Methylation cytosine residues genomic DNA is a key mark that modulates gene expression prevents genome instability. Here, we report test the relationship between replication methylation context vertebrate organism instead cell lines. Our analysis based identification hypomorphic alleles dnmt1 , encoding maintenance methylase Dnmt1, pole1...
The thymus is a lymphoid organ unique to vertebrates, and it provides microenvironment that facilitates the differentiation of immature hematopoietic precursors into mature T cells. We subjected evolutionary trajectory thymic experimental analysis. A hypothetical primordial form was established in mice by replacing FOXN1, vertebrate-specific master regulator epithelial cell function, with its metazoan ancestor, FOXN4, thereby resetting regulatory coding changes have occurred since divergence...
Recent work on vertebrate hematopoiesis has uncovered the presence of deeply rooted similarities between fish and mammals at molecular cellular levels. Although small animal models such as zebrafish are ideally suited for genetic chemical screens, study aspects hematopoietic development in lower vertebrates is severely hampered by complex nature their histocompatibility-determining genes. Hence, even when hosts sublethally irradiated before cell transplantation, stable long-term...
Significance The alternative adaptive immune system of jawless vertebrates is based on three types variable lymphocyte receptors (VLRs) that are differentially expressed by distinct B- and T-like lineages. Like the antibodies T-cell jawed vertebrates, highly VLR antigen generated combinatorial assembly. However, it not known whether VLRs subjected to selection mitigate detrimental effects self-reactivity. Here, we identify signatures for VLRC one lineages lamprey; concerns length receptor...
Lymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility non-mammalian models to define molecular basis their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell revealed several major pathways. The identification lineage-specific transcription factors specific cytokine signaling DNA replication and/or repair pathways known from studies immunocompromised mammals provided an...
The antibodies of jawless vertebrates consist leucine-rich repeat arrays encoded by somatically assembled VLRB genes. It is unknown how the incomplete germline loci are converted into functional antibody genes during B lymphocyte development in lampreys. In Lampetra planeri larvae lacking cytidine deaminase CDA2 gene, assembly fails, whereas T lineage-associated VLRA and VLRC antigen receptor gene assemblies occur normally. Thus, acts a cell lineage-specific fashion to support somatic...