Modifying transcript lengths of cycling mouse segmentation genes

Autor: Christine Laclef, Michael Stauber, David Ish-Horowicz, Mahalia E. Page, Annalisa Vezzaro
Přispěvatelé: Laclef, Christine, Cancer Research UK London Research Institute, Morphogénèse du Cerveau des Vertébrés = Morphogenesis of the vertebrate brain (LBD-E10), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University College of London [London] (UCL)
Rok vydání: 2011
Předmět:
Embryology
Mice
129 Strain
Notch signaling pathway
Mice
Transgenic
[SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics
Biology
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
LFNG
03 medical and health sciences
Mice
0302 clinical medicine
Somitogenesis
[SDV.BDD] Life Sciences [q-bio]/Development Biology
medicine
Paraxial mesoderm
Basic Helix-Loop-Helix Transcription Factors
Animals
Protein Isoforms
Gene Knock-In Techniques
RNA
Messenger
[SDV.BDD]Life Sciences [q-bio]/Development Biology
030304 developmental biology
Body Patterning
Genetics
0303 health sciences
Alternative splicing
Intron
Gene Expression Regulation
Developmental
Glycosyltransferases
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
[SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular Networks [q-bio.MN]
Embryo
Mammalian
Cell biology
Mice
Inbred C57BL
Somite
[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics
Alternative Splicing
medicine.anatomical_structure
[SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular Networks [q-bio.MN]
Somites
RNA splicing
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Mechanisms of Development
Mechanisms of Development, 2012, 129 (1-4), pp.61-72. ⟨10.1016/j.mod.2012.01.006⟩
Mechanisms of Development, Elsevier, 2012, 129 (1-4), pp.61-72. ⟨10.1016/j.mod.2012.01.006⟩
ISSN: 1872-6356
0925-4773
DOI: 10.1016/j.mod.2012.01.006⟩
Popis: International audience; Segmentation Transcriptional elongation Timing Oscillators Pattern formation A B S T R A C T Regular production of somites, precursors of the axial skeleton and attached muscles is controlled by a molecular oscillator, the segmentation clock, which drives cyclic transcription of target genes in the unsegmented presomitic mesoderm (PSM). The clock is based on a negative feedback loop which generates pulses of transcription that oscillate with the same periodicity as somite formation. Mutants in several oscillating genes including the Notch pathway gene Lunatic fringe (Lfng) and the Notch target Hes7, result in defective somitogen-esis and disorganised axial skeletons. Both genes encode negative regulators of Notch signalling output, but it is not yet clear if they are just secondary clock targets or if they encode components of a primary, pacemaker oscillator. In this paper, we try to identify components in the primary oscillator by manipulating delays in the feedback circuitry. We characterise recombinant mice in which Lfng and Hes7 introns are lengthened in order to delay mRNA production. Lengthening the third Hes7 intron by 10 or 20 kb disrupts accurate RNA splicing and inactivates the gene. Lfng expression and activity is normal in mice whose Lfng is lengthened by 10 kb, but no effects on segmentation are evident. We discuss these results in terms of the relative contributions of transcriptional and post-transcriptional delays towards defining the pace of segmenta-tion, and of alternative strategies for manipulating the period of the clock.
Databáze: OpenAIRE
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