Dynamic expression and essential functions of <i>Hes7</i> in somite segmentation

Bessho, Yasumasa; Sakata, Ryoichi; Komatsu, Shintaro; Shiota, Kohei; Yamada, Shuichi; Kageyama, Ryoichiro

doi:10.1101/gad.930601

Cited by 339 publications

(353 citation statements)

References 32 publications

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“…Hes7 is a segmentation clock gene involved in somitogenesis of embryos (Bessho, et al, 2001a;Bessho, et al, 2001b). Somites are metameric structures periodically segmented from the anterior parts of the presomitic mesoderm.…”

Section: Forced Expression Of Hes1 Results In Increased Numbers Of Qumentioning

confidence: 99%

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: Forced Expression Of Hes1 Results In Increased Numbers Of Qumentioning

confidence: 99%

Expression Dynamics and Functions of Hes Factors in Development and Diseases

Kobayashi

Kageyama

2014

Current Topics in Developmental Biology

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“…In addition, Lunatic fringe, encoding a glycosyltransferase that modulates the Notch signaling in the chicken and mouse, and the Notch ligand deltaC in the zebrafish also show an oscillatory expression pattern in the PSM. These cyclic genes, as well as other components of the Notch signaling pathway, were shown to be required for the proper somite segmentation in mice (Hrabe de Angelis et al 1997;Kusumi et al 1998;Bessho et al 2001) and zebrafish (Takke and CamposOrtega 1999;Holley et al 2000Holley et al , 2002Henry et al 2002;Oates and Ho 2002) by mutant analysis or morpholino oligo (MO)-mediated gene-knockdown experiments. Furthermore, the cyclic expression of Hes7, her1, and her7 requires their own activity, suggesting that a negative feedback loop involving these genes is a critical component of the oscillation machinery (Oates and Ho 2002;.…”

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Zebrafish Hairy/Enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites

Kawamura¹,

Koshida²,

Hijikata³

et al. 2005

Genes Dev.

111

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Notch and fibroblast growth factor (FGF) signaling pathways have been implicated in the establishmentSomites are the morphologically distinct segmental units that are transiently formed during early vertebrate development and subsequently give rise to metameric and fundamental structures such as the vertebrae of the axial skeleton, their associated muscles, and tendons. The somites are subdivided from the anterior end of the unsegmented paraxial mesoderm, called the presomitic mesoderm (PSM), and sequentially generated in an anterior to posterior direction in a rhythmic fashion at regular spatiotemporal intervals. The molecular mechanism underlying the periodical formation of somites is coupled to an internal oscillator, referred to as the "segmentation clock", which has been evidenced by the cyclic expression of genes in the PSM (Palmeirim et al. 1997;Maroto and Pourquie 2001). Most genes that exhibit a cyclic expression pattern in the PSM are involved in the Notch signaling pathway . Various hairy/Enhancer of split (Espl)-related basic helix-loop-helix (bHLH) genes (hairy-1, hairy-2, and Hey2 in the chicken; Hes1, Hes5, Hes7, and Hey2 in the mouse; her1 and her7 in the zebrafish) that are transcriptional targets of the Notch signaling are expressed in a dynamic pattern of stripes across the PSM in a posterior to anterior direction. In addition, Lunatic fringe, encoding a glycosyltransferase that modulates the Notch signaling in the chicken and mouse, and the Notch ligand deltaC in the zebrafish also show an oscillatory expression pattern in the PSM. These cyclic genes, as well as other components of the Notch signaling pathway, were shown to be required for the proper somite segmentation in mice ( The oscillating and anteriorly propagating wave of gene expression, which is maintained in the posterior PSM, becomes fixed to cause segmentation in the anterior PSM. Activity gradients of signaling molecules, including fibroblast growth factor (FGF), Wnt, and retinoic acid are proposed to regulate the differentiation of PSM cells along the anteroposterior axis from a state permitting the oscillating gene expression to a state driving the segmentation program (Dubrulle et al. 2001;Sawada et al. 2001;Aulehla et al. 2003;Moreno and Kintner 2004). For instance, FGF signaling is the highest at the posterior end of the PSM with a gradual decrease toward the anterior, suggesting a role for FGF signaling in maintaining the characteristics of the posterior PSM cells (Dubrulle et al. 2001;Sawada et al. 2001). In fact, overexpression of FGF8 in the entire PSM of chick embryos causes an increase in the expression of Brachyury in the posterior PSM and suppresses morphological segmentation (Dubrulle et al. 2001). Furthermore, transient activation or inhibition of FGF signaling results in the formation of smaller or larger somites, respectively. Thus, FGF signaling appears to maintain the posterior characteristics, which allows the cyclic gene expression, and the level of FGF activity regulates the transition of the posterior PSM ...

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“…All of the cyclic genes identified to date encode components of the Notch and Wnt signaling pathways. In mice, these cyclic genes include Notch pathway components and modulators such as the basic he-lix-loop-helix transcription factors Hes1 (Jouve et al, 2000) and Hes7 (Bessho et al, 2001), the glycosyltransferase Lunatic fringe (Lfng; Cohen et al, 1997;Johnston et al, 1997;Forsberg et al, 1998;Aulehla and Johnson, 1999), and the Wnt pathway negative regulators axin2 (Aulehla et al, 2003) and nkd1 (Ishikawa et al, 2004).…”

Section: Segmentation Clock: a Molecular Oscillator Operating In The mentioning

confidence: 99%

The long and short of it: Somite formation in mice

Gridley

2006

Developmental Dynamics

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A fundamental characteristic of the vertebrate body plan is its segmentation along the anterior-posterior axis. This segmental pattern is established during embryogenesis by the formation of somites, the transient epithelial blocks of cells that derive from the unsegmented presomitic mesoderm. Somite formation involves a molecular oscillator, termed the segmentation clock, in combination with gradients of signaling molecules such as fibroblast growth factor 8, WNT3A, and retinoic acid. Disruption of somitogenesis in humans can result in disorders such as spondylocostal dysostosis, which is characterized by vertebral malformations. This review summarizes recent findings concerning the role of Notch signaling in the segmentation clock, the complex regulatory network that governs somitogenesis, the genes that cause inherited spondylocostal dysostosis, and the mechanisms that regulate bilaterally symmetric somite formation. Developmental Dynamics 235:2330 -2336, 2006.

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Dynamic expression and essential functions of Hes7 in somite segmentation

Cited by 339 publications

References 32 publications

Expression Dynamics and Functions of Hes Factors in Development and Diseases

Expression Dynamics and Functions of Hes Factors in Development and Diseases

Zebrafish Hairy/Enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites

The long and short of it: Somite formation in mice

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