Publications (3)8.13 Total impact
-
Article: Chromatin modification in zebrafish development.
[show abstract] [hide abstract]
ABSTRACT: The generation of complex organisms requires that an initial population of cells with identical gene expression profiles can adopt different cell fates during development by progressively diverging transcriptional programs. These programs depend on the binding of transcritional regulators to specific genomic sites, which in turn is controlled by modifications of the chromatin. Chromatin modifications may occur directly upon DNA by methylation of specific nucleotides, or may involve post-translational modification of histones. Local regulation of histone post-translational modifications regionalizes the genome into euchromatic regions, which are more accessible to DNA-binding factors, and condensed heterochromatic regions, inhibiting the binding of such factors. In addition, these modifications may be required in a genome-wide fashion for processes such as DNA replication or chromosome condensation. From an embryologist's point of view chromatin modifications are intensively studied in the context of imprinting and have more recently received increasing attention in understanding the basis of pluripotency and cellular differentiation. Here, we describe recently uncovered roles of chromatin modifications in zebrafish development and regeneration, as well as available resources and commonly used techniques. We provide a general introduction into chromatin modifications and their respective functions with a focus on gene transcription, as well as key aspects of their roles in the early zebrafish embryo, neural development, formation of the digestive system and tissue regeneration.Methods in cell biology 01/2011; 104:401-28. · 2.05 Impact Factor -
Article: Analysis of the Albumin/alpha-Fetoprotein/Afamin/Group specific component gene family in the context of zebrafish liver differentiation.
[show abstract] [hide abstract]
ABSTRACT: Members of the Albumin/alpha-Fetoprotein/Afamin/Group specific component (Alb/Afp/Afm/Gc) multi-gene family perform physiological functions essential for body homeostasis and are among the earliest genes to be expressed in the fetal liver in mammals. A comprehensive search of the zebrafish genome has led to the isolation of a single member of this gene family, exhibiting close homology to group specific component (gc; also described as vitamin D binding protein (dbp)). Our phylogenetic analyses did not uncover albumin in the genome, indicating its likely absence in zebrafish, whereas the absence of afp and afm is in agreement with previous findings that both genes arose at a later stage of vertebrate evolution. gc mRNA expression is initiated weakly around 55 hours post fertilisation (hpf) in the developing liver, and increases until it reaches a continuously high level from about 72 hpf onwards. Investigation of gc mRNA in hdac1 mutants revealed a severe delay of expression, indicating a defect in progression of hepatic differentiation. This provides further evidence for Hdac1 regulating the precise timely execution of hepatic gene expression programmes. Conversely, onset of gc expression was unaltered in cloche mutant embryos, which lack hepatic vasculature, suggesting that this particular step of hepatic differentiation occurs independently from endothelial cells. Our studies identify gc as the likely only member of the Alb/Afp/Afm/Gc gene family in zebrafish, providing important insights into the evolution of this multi-gene family in vertebrates. Furthermore, the identification of gc adds a valuable temporal marker for investigating progressive hepatic differentiation in zebrafish.Gene Expression Patterns 09/2010; 10(6):237-43. · 2.02 Impact Factor -
Article: Organ-specific requirements for Hdac1 in liver and pancreas formation.
[show abstract] [hide abstract]
ABSTRACT: Liver, pancreas and lung originate from the presumptive foregut in temporal and spatial proximity. This requires precisely orchestrated transcriptional activation and repression of organ-specific gene expression within the same cell. Here, we show distinct roles for the chromatin remodelling factor and transcriptional repressor Histone deacetylase 1 (Hdac1) in endodermal organogenesis in zebrafish. Loss of Hdac1 causes defects in timely liver specification and in subsequent differentiation. Mosaic analyses reveal a cell-autonomous requirement for hdac1 within the hepatic endoderm. Our studies further reveal specific functions for Hdac1 in pancreas development. Loss of hdac1 causes the formation of ectopic endocrine clusters anteriorly to the main islet, as well as defects in exocrine pancreas specification and differentiation. In addition, we observe defects in extrahepatopancreatic duct formation and morphogenesis. Finally, loss of hdac1 results in an expansion of the foregut endoderm in the domain from which the liver and pancreas originate. Our genetic studies demonstrate that Hdac1 is crucial for regulating distinct steps in endodermal organogenesis. This suggests a model in which Hdac1 may directly or indirectly restrict foregut fates while promoting hepatic and exocrine pancreatic specification and differentiation, as well as pancreatic endocrine islet morphogenesis. These findings establish zebrafish as a tractable system to investigate chromatin remodelling factor functions in controlling gene expression programmes in vertebrate endodermal organogenesis.Developmental Biology 08/2008; 322(2):237-50. · 4.07 Impact Factor
Top Journals
Institutions
-
2008–2011
-
MRC National Institute for Medical Research
- Division of Developmental Biology
London, ENG, United Kingdom
-