The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite

Oginuma, Masayuki; Takahashi, Yu; Kitajima, Satoshi; Kiso, Makoto; Kanno, Jun; Kimura, Asako; Saga, Yumiko

doi:10.1242/dev.044545

Cited by 56 publications

(65 citation statements)

References 33 publications

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“…3Bg-i). This suggests that mature somitic structures are caudalized in Lfng RLFNG/+ embryos, in contrast to Lfng null embryos, which, as previously reported (Oginuma et al, 2010), exhibit a pattern of intermingled rostral and caudal cells (Fig. 3Be,h).…”

Section: Rlfng Expression Perturbs Cyclic Activity In the Notch Pathwaysupporting

confidence: 81%

“…Supporting this idea, it has been shown that either loss of Lfng activity (Evrard et al, 1998;Zhang and Gridley, 1998) or sustained, non-oscillatory Lfng expression in the PSM (Serth et al, 2003) perturbs embryonic segmentation and clock function. Lfng is also expressed in the anterior PSM, in the rostral compartment of patterning presomites (Cole et al, 2002), although most data suggest that its most important roles in segmentation are in the clock (Oginuma et al, 2010;Williams et al, 2014).…”

Section: Introductionmentioning

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: 81%

Section: Introductionmentioning

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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“…Importantly, in the mouse, Notch signaling is also essential for translating the clock message into somite A/P polarity and boundaries in region II (26,27). The intermediate NICD stripe (∼S−2/S−1) in combination with Wnt signaling near the determination front is critical (26).…”

Section: Significancementioning

confidence: 99%

Dynamic CREB family activity drives segmentation and posterior polarity specification in mammalian somitogenesis

Lopez

Fan

2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance The segmented axial skeleton of vertebrates is composed of an interlinked framework of vertebrae and ribs. During embryogenesis, vertebral precursors known as somites form sequentially from a progenitor tissue known as the presomitic mesoderm to foreshadow the metamerism of the axial skeleton. We have discovered that the cAMP responsive element binding protein (CREB) family of transcription factors operates in combination with Notch and Wnt signaling to instruct the timely scission of presomitic mesoderm into somites with proper anterior/posterior polarities. Thus, the CREB family represents a new and important molecular integrator in axial skeleton development. Our work has potential implications to spinal disorders such as scoliosis.

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“…From enhancer dissection studies of the mouse cyclic lunatic fringe (Lfng) gene, which activates Notch signaling in the PSM via glycosyltransferase activity, it has been proposed that Notch signaling is primarily required in the anterior PSM downstream of the segmentation clock (Shifley et al, 2008;Stauber et al, 2009). However, the existence of weak residual posterior PSM oscillations driven by the tested enhancer constructs (Stauber et al, 2009) and the ability of the posterior-specific cyclic regulatory region of Hes7 to rescue completely the loss of function Lfng phenotype (Oginuma et al, 2010) suggest that oscillating Notch signaling in the segmentation clock itself is essential for mouse somitogenesis. …”

mentioning

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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The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite

Cited by 56 publications

References 33 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

Dynamic CREB family activity drives segmentation and posterior polarity specification in mammalian somitogenesis

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

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