Cyclic <i>Nrarp</i> mRNA expression is regulated by the somitic oscillator but Nrarp protein levels do not oscillate

Wright, David C.; Ferjentsik, Zoltan; Chong, Shang-Wei; Qiu, Xuehui; Jiang, Yun-Jin; Malapert, Pascale; Pourquié, Olivier; Hateren, Nick Van; Wilson, Stuart A.; Franco, Cláudio A.; Gerhardt, Holger; Dale, J. Kim; Maroto, Miguel

doi:10.1002/dvdy.22139

Cited by 16 publications

(18 citation statements)

References 57 publications

(115 reference statements)

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“…This pattern of Notch activity is confirmed by the expression of Nrarp, a direct Notch target in the PSM (Dequeant et al, 2006;Wright et al, 2009), which is severely reduced in the posterior PSM of all Lfng RLFNG/+ embryos examined, with expression restricted to an anterior stripe ( Fig. 2Ca-d).…”

Section: Rlfng Expression Perturbs Cyclic Activity In the Notch Pathwaysupporting

confidence: 54%

“…In mouse embryos, targets of the FGF and WNT pathways have been observed to oscillate in the PSM (Dequeant et al, 2006;Wright et al, 2009), and it is clear that both FGF and WNT signaling are important for normal clock function (Aulehla and Pourquie, 2010). To determine whether RLFNG expression perturbs clock-linked genes in other pathways, we examined the expression patterns of Axin2, Spry2 and Snai1.…”

Section: Rlfng Expression Perturbs Cyclic Activity In the Notch Pathwaymentioning

confidence: 99%

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A novel targeted Lunatic fringe allele predicted to reduce protein secretion is dominant and disrupts somitogenesis

et al. 2016

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Vertebrate somitogenesis is regulated by a segmentation clock. Clock-linked genes exhibit cyclic expression, with a periodicity matching the rate of somite production. In mice, lunatic fringe (Lfng) expression oscillates, and LFNG protein contributes to periodic repression of Notch signaling. We hypothesized that rapid LFNG turnover could be regulated by protein processing and secretion. Here, we describe a novel Lfng allele (Lfng RLFNG ), replacing the N-terminal sequences of LFNG, which allow for protein processing and secretion, with the N-terminus of radical fringe (a Golgi-resident protein). This allele is predicted to prevent protein secretion without altering the activity of LFNG, thus increasing the intracellular half-life of the protein. This allele causes dominant skeletal and somite abnormalities that are distinct from those seen in Lfng loss-of-function embryos. Expression of clock-linked genes is perturbed and mature Hes7 transcripts are stabilized in the presomitic mesoderm of mutant mice, suggesting that both transcriptional and post-transcriptional regulation of clock components are perturbed by RLFNG expression. Contrasting phenotypes in the segmentation clock and somite patterning of mutant mice suggest that LFNG protein may have context-dependent effects on Notch activity.

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Section: Rlfng Expression Perturbs Cyclic Activity In the Notch Pathwaysupporting

confidence: 54%

Section: Rlfng Expression Perturbs Cyclic Activity In the Notch Pathwaymentioning

confidence: 99%

A novel targeted Lunatic fringe allele predicted to reduce protein secretion is dominant and disrupts somitogenesis

et al. 2016

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Section: Traveling Waves Of Cyclic Gene Expressionmentioning

confidence: 99%

“…Proteins encoded by some of these cyclic genes have oscillating levels, as shown by antibody staining (Bessho et al, 2003;Dale et al, 2003), indicating that unstable mRNA and proteins of cyclic genes are expressed and degraded in every cycle of the segmentation clock. Nevertheless, protein levels from very few cyclic genes have been measured, and it remains to be seen how many exhibit meaningful protein oscillations (Wright et al, 2009).The key observable features of these oscillating patterns are: (1) a traveling wave of gene expression moving anteriorly through the PSM; (2) the slowing and shortening of the wave in the AP direction, and its arrest in the anterior of the PSM at a position that prefigures prospective somite boundaries; and (3) the repetition of the pattern with the formation of each new somite pair. These properties of the traveling wave patterns have been confirmed by time-lapse microscopy in living mouse embryos using luminescent The circadian clock is probably the best-understood biological clock (Hogenesch and Ueda, 2011).…”

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confidence: 99%

Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock

2012

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The segmentation clock is an oscillating genetic network thought to govern the rhythmic and sequential subdivision of the elongating body axis of the vertebrate embryo into somites: the precursors of the segmented vertebral column. Understanding how the rhythmic signal arises, how it achieves precision and how it patterns the embryo remain challenging issues. Recent work has provided evidence of how the period of the segmentation clock is regulated and how this affects the anatomy of the embryo. The ongoing development of realtime clock reporters and mathematical models promise novel insight into the dynamic behavior of the clock.Key words: Gradient, Modeling, Negative feedback, Oscillator, Signaling, Somitogenesis IntroductionThe segmented anatomy of the vertebrate embryo is evident in the two bilaterally symmetrical rows of somites that flank the notochord along the body axis. These blocks of mesodermal cells give rise primarily to bone, muscle and skin of the adult body, which is correspondingly segmented. Somitogenesis is a rhythmic and sequential process in which each successive bilateral somite pair segregates at a regular time interval from the anterior end of the pre-somitic mesoderm (PSM, see Glossary, Box 1) as the body axis elongates (Fig. 1A,B). Somitogenesis has long been of interest to developmental biologists because it involves the coordination of patterning and growth of a tissue by a regularly repeated morphogenetic process. The topic of this review is the molecular segmentation clock that underlies this periodicity. The segmentation clock has attracted the attention of those interested in biological clocks and the molecular mechanisms of developmental timing, as well as those studying the function and stability of rapidly acting genetic circuits, and the interplay between the properties of single cells and their collective behavior at the tissue level. Finally, the rhythmic nature of the process is the seed for a theoretical interest in somitogenesis that is decades old and now promises a powerful synthesis of experiment and theory that is emblematic of modern embryology.This review first provides an overview of somitogenesis, then describes the prevailing dynamic model for somitogenesis, the Clock and Wavefront mechanism, its molecular phenomenology Development 139, 625-639 (2012) REVIEW Box 1. GlossaryBiological oscillator. A system that generates a periodic variation in the state of a cell, tissue or organism. The vibrating stereocillia bundles of inner ear hair cells, the contraction cycle of cardiac muscle cells, circadian clocks and rhythmic neuronal circuits are all biological oscillators. Coupling. Communication between neighboring oscillators that leads to mutual adjustment of their frequencies. For example, activation of Notch receptors in a presomitic mesoderm cell by Delta from neighboring cells can affect the dynamics of Notch pathway components in the target cell. Frequency profile. Dependence of the frequency of the oscillators in an array on their position. In the segmentat...

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“…Many of these genes encode negative-feedback inhibitors of the pathways, and current models suggest that these feedbacks might be important for oscillations (Goldbeter and Pourquie, 2008;Lewis, 2003). Cyclic genes have also been identified by a candidate gene approach in other species such as chicken (Aulehla and Johnson, 1999;Dale et al, 2006;Jouve et al, 2000;Leimeister et al, 2000;McGrew et al, 1998;Palmeirim et al, 1997;Wright et al, 2009), zebrafish (Henry et al, 2002;Holley et al, 2000;Jiang et al, 2000;Oates and Ho, 2002;Shankaran et al, 2007;Sieger et al, 2004) and Xenopus (Li et al, 2003), indicating an evolutionary conservation of the segmentation clock in vertebrates. In these species, the few known cyclic genes mostly belong to the Notch pathway, including members of the Hairy and enhancer of split (Hes/Her) family of bHLH transcription factors and the Notch glycosyl transferase lunatic fringe (Lfng).…”

Section: Introductionmentioning

confidence: 99%

Evolutionary plasticity of segmentation clock networks

et al. 2011

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SUMMARYThe vertebral column is a conserved anatomical structure that defines the vertebrate phylum. The periodic or segmental pattern of the vertebral column is established early in development when the vertebral precursors, the somites, are rhythmically produced from presomitic mesoderm (PSM). This rhythmic activity is controlled by a segmentation clock that is associated with the periodic transcription of cyclic genes in the PSM. Comparison of the mouse, chicken and zebrafish PSM oscillatory transcriptomes revealed networks of 40 to 100 cyclic genes mostly involved in Notch, Wnt and FGF signaling pathways. However, despite this conserved signaling oscillation, the identity of individual cyclic genes mostly differed between the three species, indicating a surprising evolutionary plasticity of the segmentation networks. the GeneChip Eukaryotic Small Sample Target Labeling Assay version II, and the second cycle of the Two-Cycle Eukaryotic Target Labeling Assay, as described in the Affymetrix GeneChip Expression Analysis Technical Manual rev5. Amplified RNA samples were hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 arrays. For chicken and zebrafish, total RNA was extracted from PSM pieces using Trizol. PSM pieces contained ~4000 chicken cells or ~400 zebrafish cells. The mRNA of each sample was amplified following a two-cycle linear amplification protocol as described in the Two-Cycle Eukaryotic Target Labeling Assay in the Affymetrix GeneChip Expression Analysis Technical Manual rev5. Briefly, cDNA was synthesized from total RNA using T7 linked to oligo(dT) primers. After second-strand synthesis, cRNA was in vitro transcribed using unlabeled ribonucleotides. Upon a second round of cDNA synthesis using random priming, cRNA was made with biotin-labeled CTP and UTP, yielding 35-135 g of biotinylated cRNA for chicken and 3-6 g for zebrafish. RNA quality was checked after the second round of amplification by measuring the A 260 /A 280 ratio (which ranged from 1.8 to 2.1) and the fragment size with the Agilent Bioanalyser (mean size >1 kb). Five micrograms of RNA from good quality samples was fragmented to less than 200 bp, hybridized to Affymetrix GeneChip chicken genome arrays or GeneChip zebrafish genome arrays according to manufacturer's instructions and scanned with a GeneArray scanner (Agilent G2500A) at the Microarray Core Facility of the Stowers Institute for Medical Research. The array readout was processed using Affymetrix Microarray Suite (MAS) 5.0 and scaled by adjusting the average intensity of each array to a target intensity of 150. The quality control parameters from the Affymetrix array reports were within acceptable limits and highly similar between the arrays. The raw data are available on ArrayExpress with accession E-MTAB-406. Non-biological variance of the microarrays was controlled by two methods: the R package affyPLM (Bolstad et al., 2005) using the normalized unscaled standard error (NUSE) and relative expression (RLE) functions; and principal component analysis (PCA) using Partek ...

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Cyclic Nrarp mRNA expression is regulated by the somitic oscillator but Nrarp protein levels do not oscillate

Cited by 16 publications

References 57 publications

A novel targeted Lunatic fringe allele predicted to reduce protein secretion is dominant and disrupts somitogenesis

A novel targeted Lunatic fringe allele predicted to reduce protein secretion is dominant and disrupts somitogenesis

Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock

Evolutionary plasticity of segmentation clock networks

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