RhoA and microtubule dynamics control cell–basement membrane interaction in EMT during gastrulation

Nakaya, Yukiko; Sukowati, Erike W.; Wu, Yuping; Sheng, Guojun

doi:10.1038/ncb1739

Cited by 255 publications

(265 citation statements)

References 47 publications

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“…1A, B), immunostaining for Ecadherin was strong on the whole surface of all superficial epithelial cells both in the nascent neural plate and in the non-induced epiblast. No Ecadherin was found in the mesoderm, but, as shown previously (Nakaya et al, 2008;Hardy et al, 2011), it was detectable in the primitive streak, in both ingressing and early migrating mesodermal cells. N-cadherin exhibited a reciprocal pattern to E-cadherin, with a strong expression in the mesoderm and a complete exclusion from the neural plate and the epiblast.…”

Section: Timing and Kinetics Of E-to N-cadherin Switch During Early Nsupporting

confidence: 79%

“…The slow replacement of E-cadherin by N-cadherin in the neural plate contrasts strikingly with the situation found in the primitive streak, where ingressing mesodermal cells express Snail-2 and Brachyury and immediately execute a complete EMT program with breakdown of the basement membrane, loss of cell polarity, and a rapid E-to N-cadherin switch (Sefton et al, 1998;Nakaya et al, 2008;Acloque et al, 2011). Beside Snail-1, Snail-2 is considered as the prototype of EMT inducers.…”

Section: Fig 2 Expression Patterns Of E-and N-cadherins and Their Tmentioning

confidence: 93%

“…In particular, the switch between E-and N-cadherin has been found to play a key role in early morphogenesis and in pathological situations, by promoting the process of epithelium-to-mesenchyme transition (EMT; Wheelock et al, 2008;Thiery et al, 2009). During gastrulation, for example, N-cadherin is up-regulated at the expense of E-cadherin on the surface of nascent mesodermal cells ingressing from the superficial ectoderm into the primitive streak (Ohta et al, 2007;Nakaya et al, 2008;Hardy et al, 2011). Similarly, dissemination of carcinoma cells from primary epithelial tumors is often associated with E-cadherin loss combined with N-cadherin expression, and inappropriate N-cadherin up-regulation in tumor epithelial cells has been shown to promote motility and invasion (Thiery et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

Dady

Blavet

Duband

2012

Developmental Dynamics

107

132

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Background: During embryonic development, cadherin switches are correlated with tissue remodelings, such as epithelium-to-mesenchyme transition (EMT). An E-to N-cadherin switch also occurs during neurogenesis, but this is not accompanied with EMT. The biological significance of this switch is currently unknown. Results: We analyzed the timing and kinetics of the E-to N-cadherin switch during early neural induction and neurulation in the chick embryo, in relation to the patterns of their transcriptional regulators. We found that deployment of the E-to N-cadherin switch program varies considerably along the embryonic axis. Rostrally in regions of primary neurulation, it occurs progressively both in time and space in a manner that appears neither in connection with morphological transformation of neural epithelial cells nor in synchrony with movements of neurulation. Caudally, in regions of secondary neurulation, neurogenesis was not associated with cadherin switch as N-cadherin pre-existed before formation of the neural tube. We also found that, during neural development, cadherin switch is orchestrated by a set of transcriptional regulators distinct from those involved in EMT. Conclusions: Our results indicate that cadherin switch correlates with the partition of the neurectoderm into its three main populations: ectoderm, neural crest, and neural tube.

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Section: Timing and Kinetics Of E-to N-cadherin Switch During Early Nsupporting

confidence: 79%

Section: Fig 2 Expression Patterns Of E-and N-cadherins and Their Tmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

Dady

Blavet

Duband

2012

Developmental Dynamics

107

132

View full text Add to dashboard Cite

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“…The picture emerging from diverse EMT-related studies suggests that precise molecular and cellular control of EMT is complex and context-dependent (Nakaya et al, 2008). An example of developmentally regulated EMT occurs during the initial stages of cardiac morphogenesis.…”

Section: Introductionmentioning

confidence: 99%

Zyxin Mediates Actin Fiber Reorganization in Epithelial–Mesenchymal Transition and Contributes to Endocardial Morphogenesis

Mori

Nakagami

Koibuchi

et al. 2009

MBoC

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Epithelial-mesenchymal transition (EMT) confers destabilization of cell-cell adhesion and cell motility required for morphogenesis or cancer metastasis. Here we report that zyxin, a focal adhesion-associated LIM protein, is essential for actin reorganization for cell migration in TGF-␤1-induced EMT in normal murine mammary gland (NMuMG) cells. TGF-␤1 induced the relocation of zyxin from focal adhesions to actin fibers. In addition, TGF-␤1 up-regulated zyxin via a transcription factor, Twist1. Depletion of either zyxin or Twist1 abrogated the TGF-␤1-dependent EMT, including enhanced cell motility and actin reorganization, indicating the TGF-␤1-Twist1-zyxin signal for EMT. Both zyxin and Twist1 were predominantly expressed in the cardiac atrioventricular canal (AVC) that undergoes EMT during heart development. We further performed ex vivo AVC explant assay and revealed that zyxin was required for the reorganization of actin fibers and migration of the endocardial cells. Thus, zyxin reorganizes actin fibers and enhances cell motility in response to TGF-␤1, thereby regulating EMT. INTRODUCTIONEpithelial-mesenchymal transition (EMT) is an essential event during embryogenesis for the formation of many tissues including the mesoderm, for migration of neural crest cells, and for development of the heart valves and septa. The picture emerging from diverse EMT-related studies suggests that precise molecular and cellular control of EMT is complex and context-dependent (Nakaya et al., 2008). An example of developmentally regulated EMT occurs during the initial stages of cardiac morphogenesis. At embryonic day 9.5 (E9.5), endocardial cells undergo EMT ("endocardial EMT"); delaminating from the endothelial sheet, invading the matrix tissue called cardiac jelly, and engaging in endocardial cushion cellularization required for valve and septum formation (Chang et al., 2004). Because a number of congenital heart diseases are caused by abnormal atrioventricular canal (AVC) development (Bruneau, 2008), understanding of the molecular basis of AVC morphogenesis has been long sought, but still not fully achieved. Several EMTinducing transcription factors such as Snail (Cano et al., 2000) and Twist1 (Ma et al., 2005) are expressed in endocardium during development. Although among them, Twist1 is well analyzed as a potent EMT inducer during cancer metastasis (Yang et al., 2004); however, the role for Twist1 in AVC development is not fully understood.An important hallmark of EMT is an increase in cell motility with actin cytoskeletal rearrangement. On EMT induction, the structure of actin cytoskeleton changes dynamically from cortical actin network to stress fiber (Zavadil and Bottinger, 2005). Cell motility also depends on the adhesion of the cell to the substratum where the integrin family molecules bind to the extracellular matrix to form focal adhesion complexes. Stress fibers link the focal adhesion to retract the cells. Furthermore, the nascent focal complexes at the leading edge of the migrating cells are needed for cell crawlin...

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“…In Xenopus, Net1 associates with Dishevelled and activates RhoA to regulate gastrulation [38]. In chick gastrulation-stage embryos, reducing Net1 or RhoA expression in epiblast cells prior to the epithelial-to-mesenchymal transition (EMT) leads to ingression and migration defects [39]. In mouse embryos, net1-deficient mammary glands exhibit decreased RhoA-mediated phosphorylation of the regulatory subunits of myosin light chain and myosin light-chain phosphatase, which results in reduced and disorganized ductal branching [40].…”

Section: Introductionmentioning

confidence: 99%

The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation

et al. 2016

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Wnt/β-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal β-catenin accumulates in dorsal marginal nuclei during cleavage stages, but its critical target genes essential for dorsalization are silent until mid-blastula transition (MBT). Here, we find that zebrafish net1, a guanine nucleotide exchange factor, is specifically expressed in dorsal marginal blastomeres after MBT, and acts as a zygotic factor to promote the specification of dorsal cell fates. Loss-and gain-of-function experiments show that the GEF activity of Net1 is required for the activation of Wnt/β-catenin signaling in zebrafish embryos and mammalian cells. Net1 dissociates and activates PAK1 dimers, and PAK1 kinase activation causes phosphorylation of S675 of β-catenin after MBT, which ultimately leads to the transcription of downstream target genes. In summary, our results reveal that Net1-regulated β-catenin activation plays a crucial role in the dorsal axis formation during zebrafish development.

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RhoA and microtubule dynamics control cell–basement membrane interaction in EMT during gastrulation

Cited by 255 publications

References 47 publications

Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

Zyxin Mediates Actin Fiber Reorganization in Epithelial–Mesenchymal Transition and Contributes to Endocardial Morphogenesis

The guanine nucleotide exchange factor Net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation

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