Left–Right Asymmetric Expression of lefty2 and nodal Is Induced by a Signaling Pathway that Includes the Transcription Factor FAST2

Saijoh, Yukio; Adachi, Hitoshi; Sakuma, Rui; Yeo, Chang Yeol; Yashiro, Kenta; Watanabe, Minoru; Hashiguchi, Hiromi; Mochida, Kyoko; Oh‐ishi, Sachiko; Kawabata, Masahiro; Miyazono, Kohei; Whitman, Malcolm; Hamada, Hiroshi

doi:10.1016/s1097-2765(00)80401-3

Cited by 218 publications

(221 citation statements)

References 66 publications

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“…Rabbit LP explant cultures isolated before the onset of PNC Nodal transcription never initiated LPM Nodal (not shown), in agreement with corresponding genetic data in mouse (Brennan et al, 2002;Saijoh et al, 2003). In that setting, the role of an inhibitor on both sides falls upon FGF8, which acts to prevent the initiation of the autoregulatory Nodal feedback loop, in which Nodal signaling induces Nodal transcription (Saijoh et al, 2000;Hamada et al, 2002, Ohi andWright, 2007). Mechanistically, this process might be accomplished by ERK-mediated phosphorylation of the linker domain of SMAD2, which inhibits Nodal signal transduction (Massague, 2003;Pera et al, 2003).…”

Section: Discussionsupporting

confidence: 84%

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Feistel

Blum

2008

Developmental Dynamics

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Section: Discussionsupporting

confidence: 84%

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Feistel

Blum

2008

Developmental Dynamics

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“…Likewise, Lefty2, the expression of which we found missing in the primitive streak and nascent mesoderm cells of E7.0-E7.5 N1ICD epi embryos (n=11; Fig. 6L,L′), is a direct target of NODAL signalling (Saijoh et al, 2000). Our analysis therefore indicates that over-activating the NOTCH pathway in the epiblast results in defects normally associated with a dampening of NODAL signalling.…”

Section: Notch Activation Impairs Axial Mesoderm Formation and Perturmentioning

confidence: 55%

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

et al. 2015

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NOTCH signalling is an evolutionarily conserved pathway involved in intercellular communication essential for cell fate choices during development. Although dispensable for early aspects of mouse development, canonical RBPJ-dependent NOTCH signalling has been shown to influence lineage commitment during embryonic stem cell (ESC) differentiation. NOTCH activation in ESCs promotes the acquisition of a neural fate, whereas its suppression favours their differentiation into cardiomyocytes. This suggests that NOTCH signalling is implicated in the acquisition of distinct embryonic fates at early stages of mammalian development. In order to investigate in vivo such a role for NOTCH signalling in shaping cell fate specification, we use genetic approaches to constitutively activate the NOTCH pathway in the mouse embryo. Early embryonic development, including the establishment of anterior-posterior polarity, is not perturbed by forced NOTCH activation. By contrast, widespread NOTCH activity in the epiblast triggers dramatic gastrulation defects. These are fully rescued in a RBPJ-deficient background. Epiblast-specific NOTCH activation induces acquisition of neurectoderm identity and disrupts the formation of specific mesodermal precursors including the derivatives of the anterior primitive streak, the mouse organiser. In addition, we show that forced NOTCH activation results in misregulation of NODAL signalling, a major determinant of early embryonic patterning. Our study reveals a previously unidentified role for canonical NOTCH signalling during mammalian gastrulation. It also exemplifies how in vivo studies can shed light on the mechanisms underlying cell fate specification during in vitro directed differentiation.

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“…The asymmetric expression of Nodal in the left LPM is governed by the intronic enhancer (ASE) element within the first intron of Nodal that is Foxh1 dependent (Norris and Robertson, 1999;Saijoh et al, 2000). Targeted deletion of this 596-bp enhancer sequence involved homologous recombination in ES cells replacing the ASE with a lox-flanked PGK-hygromycin cassette which was subsequently excised by Cre-mediated recombination resulting in the Nodal ⌬600 allele.…”

Section: Nodal ⌬600 Micementioning

confidence: 99%

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

Lu¹,

Seeholzer²,

Han³

et al. 2008

Developmental Dynamics

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Flectin, a protein previously described to be expressed in a left-dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC-II) protein class. During looping, both NMHC-IIA and NMHC-IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC-IIB, rather than NMHC-IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full-length human NMHC-IIA and -IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC-IIB antibody does not. Abnormally looping hearts of the Nodal ⌬ 600 homozygous mouse embryos show decreased NMHC-IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC-II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping. Developmental Dynamics 237:3577-3590, 2008.

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Left–Right Asymmetric Expression of lefty2 and nodal Is Induced by a Signaling Pathway that Includes the Transcription Factor FAST2

Cited by 218 publications

References 66 publications

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

NOTCH activation interferes with cell fate specification in the gastrulating mouse embryo

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

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