FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis

Naiche, L.A.; Holder, Nakisha D.; Lewandoski, Mark

doi:10.1073/pnas.1007417108

Cited by 158 publications

(204 citation statements)

References 47 publications

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“…S7), indicated an overall reduction in Wnt activity in mutant embryos. Wnt and Fgf signaling positively reinforce one another in the mouse tailbud (50)(51)(52), and consistent with diminished Wnt activity in miR-196 mutants, we also observed a down-regulation of the Fgf8 ligand and numerous Fgf downstream effectors (Fig. 6).…”

Section: Mir-196 Activity Is Required For Signaling Pathways Associatsupporting

confidence: 84%

Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs

Wong

Agarwal

Mansfield

et al. 2015

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

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The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3′ UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae.

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Section: Mir-196 Activity Is Required For Signaling Pathways Associatsupporting

confidence: 84%

Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs

Wong

Agarwal

Mansfield

et al. 2015

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

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“…Recently, Fgf4 and Fgf8 were shown to be redundant in maintaining somitogenesis in the developing mouse embryo (Naiche et al, 2011). It is conceivable that both factors together also promote formation of the WD in the intermediate mesoderm.…”

Section: Research Articlementioning

confidence: 99%

FGF8 is essential for formation of the ductal system in the male reproductive tract

et al. 2011

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SUMMARYDuring development of the urogenital tract, fibroblast growth factor 8 (Fgf8) is expressed in mesonephric tubules, but its role in this tissue remains undefined. An evaluation of previously generated T-Cre-mediated Fgf8-deficient mice (T-Cre; Fgf8 flox/D2,3 mice), which lack Fgf8 expression in the mesoderm, revealed that the cranial region of the Wolffian duct degenerated prematurely and the cranial mesonephric tubules were missing. As a result, the epididymis, vas deferens and efferent ductules were largely absent in mutant mice. Rarb2-Cre was used to eliminate FGF8 from the mesonephric tubules but to allow expression in the adjacent somites. These mutants retained the cranial end of the Wolffian duct and formed the epididymis and vas deferens, but failed to elaborate the efferent ductules, indicating that Fgf8 expression by the mesonephric tubules is required specifically for the formation of the ductules. Ret knockout mice do not form the ureteric bud, a caudal outgrowth of the Wolffian duct and progenitor for the collecting duct network in the kidney, but they do develop the cranial end normally. This indicates that Fgf8, but not Ret, expression is essential to the outgrowth of the cranial mesonephric tubules from the Wolffian duct and to the development of major portions of the sex accessory tissues in the male reproductive tract. Mechanistically, FGF8 functions upstream of Lhx1 expression in forming the nephron, and analysis of Fgf8 mutants similarly shows deficient Lhx1 expression in the mesonephric tubules. These results demonstrate a multifocal requirement for FGF8 in establishing the male reproductive tract ducts and implicate Lhx1 signaling in tubule elongation.

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“…observed in mesoderm patterning (Naiche et al, 2011;Boulet and Capecchi, 2012). Whereas single-knockout embryos form normal somites, Fgf4;Fgf8 double-knockout embryos show important axial elongation and somitogenesis defects accompanied by premature differentiation of PSM cells toward the somitic fate (Naiche et al, 2011;Boulet and Capecchi, 2012).…”

Section: Chx) (B) Qrt-pcr For Msgn1 Andmentioning

confidence: 99%

“…Whereas single-knockout embryos form normal somites, Fgf4;Fgf8 double-knockout embryos show important axial elongation and somitogenesis defects accompanied by premature differentiation of PSM cells toward the somitic fate (Naiche et al, 2011;Boulet and Capecchi, 2012). Hence, it is possible that Fgf4 has a dual function during mesodermal cell maturation.…”

Section: Chx) (B) Qrt-pcr For Msgn1 Andmentioning

confidence: 99%

Bmp signaling maintains a mesoderm progenitor cell state in the mouse tailbud

Sharma¹,

Shafer²,

Bareke³

et al. 2017

Journal of Cell Science

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Caudal somites are generated from a pool of progenitor cells located in the tailbud region. These progenitor cells form the presomitic mesoderm that gradually differentiates into somites under the action of the segmentation clock. The signals responsible for tailbud mesoderm progenitor pool maintenance during axial elongation are still elusive. Here, we show that Bmp signaling is sufficient to activate the entire mesoderm progenitor gene signature in primary cultures of caudal mesoderm cells. Bmp signaling acts through the key regulatory genes brachyury (T ) and Nkx1-2 and contributes to the activation of several other regulators of the mesoderm progenitor gene network. In the absence of Bmp signaling, tailbud mesoderm progenitor cells acquire aberrant gene expression signatures of the heart, blood, muscle and skeletal embryonic lineages. Treatment of embryos with the Bmp inhibitor noggin confirmed the requirement for Bmp signaling for normal T expression and the prevention of abnormal lineage marker activation. Together, these results identify Bmp signaling as a non-cell-autonomous signal necessary for mesoderm progenitor cell homeostasis.

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FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis

Cited by 158 publications

References 47 publications

Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs

Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs

FGF8 is essential for formation of the ductal system in the male reproductive tract

Bmp signaling maintains a mesoderm progenitor cell state in the mouse tailbud

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