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- W1515405449 abstract "The digestive system is derived from the endoderm, consisting of the alimentarycanal and its associated organs: liver, gall bladder and pancreas. Despite theessential functions of the liver, comparatively little is known about the molecularnetwork controlling liver formation. In a forward genetic screen for factorsinvolved in endodermal organogenesis, the clampeds819 mutant has been identifiedand displays defects in liver size.Positional cloning has mapped the molecular lesion underlying the clampeds819mutant phenotype to structure specific recognition protein 1a (ssrp1a). Ssrp1 is acomponent of the FACT (facilitates chromatin transcription) hetero-dimer. Ssrp1regulates nucleosome stability by interacting with histones H4 and H3 and isrequired for DNA synthesis and transcription.Phenotypic analysis of ssrp1as819 mutants revealed that liver specification isunperturbed, while subsequent differentiation and growth are disrupted. Analysisof liver proliferation uncovered defects in hepatic cell cycle progression, namelyhepatoblast arrest in S-phase in ssrp1as819 mutants. These proliferation defects arefollowed by cell death, which in ssrp1as819 mutants is only partially p53dependent. Analysis of RNA synthesis showed that Ssrp1a is required for genetranscription, revealing potential differences in mRNA stability between varioustranscripts, as some cell cycle regulators are absent and p53 target genes appear toexhibit more stable transcripts. Similar defects have been determined during eyeorganogenesis in the absence of Ssrp1a, suggesting that Ssrp1a is generallyrequired during later stages of development in highly proliferative tissues.Furthermore, the late onset of the ssrp1as819 mutant phenotype is likely due tomaternal Ssrp1a or other redundant factors such as Ssrp1b. Altogether, these data for the first time show a requirement for zygotic Ssrp1a incell cycle progression within the liver and eye, and demonstrate its critical roleduring specific phases of organ growth and differentiation." @default.
- W1515405449 created "2016-06-24" @default.
- W1515405449 creator A5057751537 @default.
- W1515405449 date "2011-04-28" @default.
- W1515405449 modified "2023-09-23" @default.
- W1515405449 title "Molecular and morphological analysis of organ growthand differentiation during zebrafish embryogenesis" @default.
- W1515405449 hasPublicationYear "2011" @default.
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