P53 activity is essential for normal development in Xenopus

Wallingford, John B.; Seufert, Daniel W.; Virta, Valerie Christine; Vize, Peter D.

doi:10.1016/s0960-9822(06)00333-2

Cited by 103 publications

(86 citation statements)

References 66 publications

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“…3). This induction of tumor-like cell mass in Xenopus has previously been reported when several other genes are overexpressed in early frog embryos, including a dominant negative p53, Gli1 oncogene, and the Rel3 transcription factor (Dahmane et al, 1997;Wallingford et al, 1997;. As in other cases, ErbBs induce tumor-like protrusion most efficiently when overexpressed in the ectoderm (Fig.…”

Section: Discussionsupporting

confidence: 79%

Regulation of early Xenopus development by ErbB signaling

Nie

Chang

2005

Developmental Dynamics

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ErbB signaling has long been implicated in cancer formation and progression and is shown to regulate cell division, migration, and death during tumorigenesis. The functions of the ErbB pathway during early vertebrate embryogenesis, however, are not well understood. Here we report characterization of ErbB activities during early frog development. Gain-of-function analyses show that EGFR, ErbB2, and ErbB4 induce ectopic tumor-like cell mass that contains increased numbers of mitotic cells. Both the muscle and the neural markers are expressed in these ectopic protrusions. ErbBs also induce mesodermal markers in ectodermal explants. Loss-of-function studies using carboxyl terminal-truncated dominant-negative ErbB receptors demonstrate that blocking ErbB signals leads to defective gastrulation movements and malformation of the embryonic axis with a reduction in the head structures in early frog embryos. These data, together with the observation that ErbBs are expressed early during frog embryogenesis, suggest that ErbBs regulate cell proliferation, movements, and embryonic patterning during early Xenopus development. Developmental Dynamics 235:301-314, 2006.

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Section: Discussionsupporting

confidence: 79%

Regulation of early Xenopus development by ErbB signaling

Nie

Chang

2005

Developmental Dynamics

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“…53 This is in contrast to p53-deficient Xenopus embryos, which display compromised cell differentiation during early stages of development. [54][55][56] Here, p53 is required for proper transforming growth factor beta (TGFb) signaling and mesoderm formation, consistent with a physical interaction of p53 with Smad proteins. 55,56 The reasons for the different requirements of p53 during early mammalian, fish and amphibian development are unclear, but might be due to the presence of other p53 family members (p63, p73) in mammals and zebrafish, whereas they appear to be absent during early stages of Xenopus development.…”

Section: Disruption Of Pold1 Leads To An Upregulation Of Genes Involvmentioning

confidence: 82%

p53 deficiency rescues apoptosis and differentiation of multiple cell types in zebrafish flathead mutants deficient for zygotic DNA polymerase δ1

et al. 2005

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Cell culture work has identified the tumor suppressor p53 as a component of the S-phase checkpoint control system, while in vivo studies of this role of p53 in whole-vertebrate systems were limited. Here, we describe zebrafish mutants in the DNA polymerase delta catalytic subunit 1, based on the positional cloning of the flathead (fla) gene. fla mutants display specific defects in late proliferative zones, such as eyes, brain and cartilaginous elements of the visceral head skeleton, where cells display compromised DNA replication, followed by apoptosis, and partial or complete loss of affected tissues. Antisense-mediated knockdown of p53 in fla mutants leads to a striking rescue of all phenotypic traits, including completion of replication, survival of cells, and normal differentiation and tissue formation. This indicates that under replicationcompromised conditions, the p53 branch of the S-phase checkpoint is responsible for eliminating stalled cells that, given more time, would have otherwise finished their normal developmental program.

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“…Nerve growth factor (NGF) 1 has profound effects on the differentiation and survival of a subset of neurons, 2 which is primarily studied in PC12 cells, a model system for neuronal differentiation. 3 Upon exposure to NGF, PC12 cells cease division, extend neurites, and acquire characteristics similar to sympathetic neurons.…”

Section: Introductionmentioning

confidence: 99%

p53 is required for nerve growth factor-mediated differentiation of PC12 cells via regulation of TrkA levels

2006

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Abstractp53 is necessary for the elimination of neural cells inappropriately differentiated or in response to stimuli. However, the role of p53 in neuronal differentiation is not certain. Here, we showed that nerve growth factor (NGF)-mediated differentiation in PC12 cells is enhanced by overexpression of wild-type p53 but inhibited by mutant p53 or knockdown of endogenous wild-type p53, the latter of which can be rescued by expression of exogenous wild-type p53. Interestingly, p53 knockdown or overexpression of mutant p53 attenuates NGF-mediated activation of TrkA, the high-affinity receptor for NGF and a tyrosine kinase, and activation of the mitogen-activated protein kinase pathway. In addition, p53 knockdown reduces the constitutive levels of TrkA, which renders PC12 cells inert to NGF. And finally, we showed that both constitutive and stimuli-induced expressions of TrkA are regulated by p53 and that induction of TrkA by activated endogenous p53 enhances NGFmediated differentiation. Taken together, our data demonstrate that p53 plays a critical role in NGF-mediated neuronal differentiation in PC12 cells at least in part via regulation of TrkA levels.

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P53 activity is essential for normal development in Xenopus

Cited by 103 publications

References 66 publications

Regulation of early Xenopus development by ErbB signaling

Regulation of early Xenopus development by ErbB signaling

p53 deficiency rescues apoptosis and differentiation of multiple cell types in zebrafish flathead mutants deficient for zygotic DNA polymerase δ1

p53 is required for nerve growth factor-mediated differentiation of PC12 cells via regulation of TrkA levels

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