Ultradian Oscillations in Notch Signaling Regulate Dynamic Biological Events

Kageyama, Ryoichiro; Niwa, Yasutaka; Shimojo, Hiromi; Kobayashi, Taeko; Ohtsuka, Toshiyuki

doi:10.1016/s0070-2153(10)92010-3

Cited by 54 publications

(56 citation statements)

References 64 publications

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“…Oscillations were also reported in some signaling pathways regulating Hes factors, such as Notch, Jak-Stat, and Fgf signalings (Kageyama, et al, 2010;Niwa et al, 2007;Yoshiura et al, 2007). For example, Notch and Fgf signaling cooperatively regulate Hes7 oscillation and achieve a spatiotemporal regulation during somite segmentation events (Niwa et al, 2011).…”

Section: Discussionmentioning

confidence: 97%

Expression Dynamics and Functions of Hes Factors in Development and Diseases

Kobayashi

Kageyama

2014

Current Topics in Developmental Biology

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Hes genes, encoding basic helix-loop-helix (HLH) transcriptional repressors, are mammalian homologues of Drosophila hairy and Enhancer of split genes, both of which are required for normal neurogenesis in Drosophila. There are seven members in the human Hes family, Hes1 to Hes7, which are expressed in many tissues and play various roles mainly in development. All Hes proteins have three conserved domains: basic HLH (bHLH), Orange, and WRPW domains. The basic region binds to target DNA sequences while the HLH region forms homo-and hetero-dimers with other bHLH proteins, the Orange domain is responsible for the selection of partners during heterodimer formation, and the WRPW domain recruits co-repressors. Hes1, Hes5, and Hes7 are known as downstream effectors of canonical Notch signaling, which regulates cell differentiation via cell-cell interaction. Hes factors regulate many events in development by repressing the expression of target genes, many of which encode transcriptional activators that promote cell differentiation. For example, Hes1, Hes3, and Hes5 are highly expressed by neural stem cells, and inactivation of these genes results in insufficient maintenance of stem cell proliferation and prematurely promotes neuronal differentiation. Recently, it was shown that the expression dynamics of Hes1 plays crucial roles in proper developmental timings and fate determination steps of embryonic stem cells and neural progenitor cells. Here we discuss some key features of Hes factors in development and diseases.

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Section: Discussionmentioning

confidence: 97%

Expression Dynamics and Functions of Hes Factors in Development and Diseases

Kobayashi

Kageyama

2014

Current Topics in Developmental Biology

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“…It is not possible to review the spectrum of stem cell systems, in which Notch has been implicated, in the context of this article. However, we need to emphasize that Notch activity is pervasive and important for the differentiation, maintenance and proliferation of stem cells in almost every system examined, including stem cell lineages, intestines, haematopoietic system, germline, various epithelia, muscle, mesenchyme, nervous system, and others (Liu et al, 2010;Perdigoto and Bardin, 2013;Kageyama et al, 2010;Conboy and Rando, 2002;Conboy et al, 2003;Carlson et al, 2008).…”

Section: Notch In Stem Cellsmentioning

confidence: 99%

Notch signaling at a glance

Hori

Sen

Artavanis‐Tsakonas

2013

Journal of Cell Science

448

438

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Cell–cell interactions define a quintessential aspect of multicellular development. Metazoan morphogenesis depends on a handful of fundamental, conserved cellular interaction mechanisms, one of which is defined by the Notch signaling pathway. Signals transmitted through the Notch surface receptor have a unique developmental role: Notch signaling links the fate of one cell with that of a cellular neighbor through physical interactions between the Notch receptor and the membrane-bound ligands that are expressed in an apposing cell. The developmental outcome of Notch signals is strictly dependent on the cellular context and can influence differentiation, proliferation and apoptotic cell fates. The Notch pathway is conserved across species (Artavanis-Tsakonas et al., 1999; Bray, 2006; Kopan and Ilagan, 2009). In humans, Notch malfunction has been associated with a diverse range of diseases linked to changes in cell fate and cell proliferation including cancer (Louvi and Artavanis-Tsakonas, 2012). In this Cell Science at a Glance article and the accompanying poster we summarize the molecular biology of Notch signaling, its role in development and its relevance to disease.

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“…The association of Dl1 with lateral inhibition is a general theme in neural development (Henrique et al, 1995;Adam et al, 1998;Kageyama et al, 2010) and that of Jag1 with lateral induction Otic vesicles co-electroporated with the 12xCSL-DsRed (DSR) reporter construct and GFP (control), Dl1/GFP, Jag1/GFP or Jag1/GFP+Dl1/GFP. Ligands were used at 1 μg/μl, and total DNA was adjusted with GFP to be constant in all conditions.…”

Section: Notch Ligands: Lateral Induction and Lateral Inhibitionmentioning

confidence: 99%

“…In the inner ear, Jag1 and Dl1 are oppositely regulated by Notch signaling, which readily accounts for their association into the circuits of lateral induction and of lateral inhibition, respectively. The inhibition of Dl1 by Notch has been associated with the repressor effect of Hes/Hey genes on bHLH proneural genes (Kageyama et al, 2010), but the activation of Jag1 by Notch remains poorly understood (Katoh, 2006).…”

Section: Notch Ligands: Lateral Induction and Lateral Inhibitionmentioning

confidence: 99%

Ligand-dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear

et al. 2014

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During inner ear development, Notch exhibits two modes of operation: lateral induction, which is associated with prosensory specification, and lateral inhibition, which is involved in hair cell determination. These mechanisms depend respectively on two different ligands, jagged 1 (Jag1) and delta 1 (Dl1), that rely on a common signaling cascade initiated after Notch activation. In the chicken otocyst, expression of Jag1 and the Notch target Hey1 correlates well with lateral induction, whereas both Jag1 and Dl1 are expressed during lateral inhibition, as are Notch targets Hey1 and Hes5. Here, we show that Jag1 drives lower levels of Notch activity than Dl1, which results in the differential expression of Hey1 and Hes5. In addition, Jag1 interferes with the ability of Dl1 to elicit high levels of Notch activity. Modeling the sensory epithelium when the two ligands are expressed together shows that ligand regulation, differential signaling strength and ligand competition are crucial to allow the two modes of operation and for establishing the alternate pattern of hair cells and supporting cells. Jag1, while driving lateral induction on its own, facilitates patterning by lateral inhibition in the presence of Dl1. This novel behavior emerges from Jag1 acting as a competitive inhibitor of Dl1 for Notch signaling. Both modeling and experiments show that hair cell patterning is very robust. The model suggests that autoactivation of proneural factor Atoh1, upstream of Dl1, is a fundamental component for robustness. The results stress the importance of the levels of Notch signaling and ligand competition for Notch function.

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Ultradian Oscillations in Notch Signaling Regulate Dynamic Biological Events

Cited by 54 publications

References 64 publications

Expression Dynamics and Functions of Hes Factors in Development and Diseases

Expression Dynamics and Functions of Hes Factors in Development and Diseases

Notch signaling at a glance

Ligand-dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear

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