The Initiation and Propagation of Hes7 Oscillation Are Cooperatively Regulated by Fgf and Notch Signaling in the Somite Segmentation Clock

Niwa, Yasutaka; Masamizu, Yoshito; Liu, Tianxiao; Nakayama, Ryu; Deng, Chu‐Xia; Kageyama, Ryoichiro

doi:10.1016/j.devcel.2007.07.013

Cited by 176 publications

(193 citation statements)

References 36 publications

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“…However, three publications analyzing conditional Fgfr1 inactivation in the mouse describe loss of FGF signaling and somitogenesis defects that are milder and occur later than in our mutants (11,12,27). Importantly, one of these studies also used T-Cre, making it directly comparable with our study (11).…”

Section: Discussionmentioning

confidence: 94%

FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis

Naiche

Holder

Lewandoski

2011

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

155

187

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Somites form along the embryonic axis by sequential segmentation from the presomitic mesoderm (PSM) and differentiate into the segmented vertebral column as well as other unsegmented tissues. Somites are thought to form via the intersection of two activities known as the clock and the wavefront. Previous work has suggested that fibroblast growth factor (FGF) activity may be the wavefront signal, which maintains the PSM in an undifferentiated state. However, it is unclear which (if any) of the FGFs expressed in the PSM comprise this activity, as removal of any one gene is insufficient to disrupt early somitogenesis. Here we show that when both Fgf4 and Fgf8 are deleted in the PSM, expression of most PSM genes is absent, including cycling genes, WNT pathway genes, and markers of undifferentiated PSM. Significantly, markers of nascent somite cell fate expand throughout the PSM, demonstrating the premature differentiation of this entire tissue, a highly unusual phenotype indicative of the loss of wavefront activity. When WNT signaling is restored in mutants, PSM progenitor markers are partially restored but premature differentiation of the PSM still occurs, demonstrating that FGF signaling operates independently of WNT signaling. This study provides genetic evidence that FGFs are the wavefront signal and identifies the specific FGF ligands that encode this activity. Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue.genetic redundancy | Spry | T-Cre | axis extension | paraxial mesoderm

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Section: Discussionmentioning

confidence: 94%

FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis

Naiche

Holder

Lewandoski

2011

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

155

187

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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: 98%

“…Hes1 regulates the proliferation of neural stem/progenitor (NS) cells in the central (see below) and peripheral nervous systems under the control of these pathways. Hes7, a segmentation clock gene involved in somitogenesis, is regulated by the Notch and FGF pathways during somite segmentation (Niwa et al, 2007). Thus, many pathways regulate Hes expression in a tissue-specific manner.…”

Section: Roles Of Hes Factors In Various Tissuesmentioning

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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“…In Lfngnull mice, Hes7 expression still oscillates, although the expression is somewhat affected (Niwa et al 2007), suggesting that Hes7 oscillation does not depend on Lfng oscillation. In contrast, in Hes7-null mice, Lfng is constitutively expressed throughout the PSM (Bessho et al 2001b).…”

Section: The Roles and The Mechanism Of Hes7 Oscillation In The Segmementioning

confidence: 99%

“…Cells experiencing the first three cycles are located in the posterior PSM, whereas those experiencing the last two cycles are located in the anterior PSM, indicating that the period of Hes1 oscillations is different between the posterior and the anterior PSM. The different periods between the posterior and the anterior PSM could be regulated by Fgf signaling (Niwa et al 2007), which forms a posterior-toanterior gradient in the PSM, although the precise mechanism remains to be determined. Hes1 expression oscillates in a stable manner in PSM cells but not in dissociated PSM cells.…”

Section: Mathematical Simulation Of Hes7 Oscillationmentioning

confidence: 99%