A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates

Plouhinec, Jean-Louis; Medina-Ruiz, Sofía; Borday, Caroline; Bernard, Elsa; Vert, Jean-Philippe; Eisen, Michael B.; Harland, Richard M.; Monsoro-Burq, Anne H.

doi:10.1371/journal.pbio.2004045

Cited by 46 publications

(71 citation statements)

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“…Melanoma initiation and progression involves the reactivation of elements belonging to the neural crest developmental program (53). We here extend the parallel between the two models, showing increased expression of PFKFB4 in development and cancer as predicted by our previous WGCNA analyses (54). Moreover, in the embryonic cells, which rely on yolk breakdown for their energy metabolism rather than on glycolysis, we have revealed the first indications for a nonconventional function of PFKFB4.…”

Section: Discussionsupporting

confidence: 86%

The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma

Sittewelle

Lécuyer

Monsoro-Burq

2020

Preprint

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Cell migration is a complex process, tightly regulated during embryonic development and abnormally activated during cancer metastasis. RAS-dependent signaling is a major nexus controlling essential cell parameters such as proliferation, survival and migration using downstream effectors among which the PI3K/AKT signaling. In melanoma, oncogenic mutations frequently enhance RAS, PI3K/AKT or MAP kinase signaling, in addition to other cancer hallmarks including the activation of metabolism regulators such as PFKFB4, a critical regulator of glycolysis and Warburg effect. Here, we explore a novel function of PFKFB4 in melanoma cell migration. We find that instead of acting as a kinase as recorded in glycolysis, PFKFB4 interacts with ICMT, a post-translational modifier of RAS. PFKFB4 promotes ICMT/RAS interaction, controls RAS addressing at the plasma membrane, activates AKT signaling and enhances cell migration. We thus evidence a novel glycolysis-independent function of PFKFB4 in human cancer cells. This unconventional activity links the metabolic regulator PFKFB4 to RAS-AKT signaling and impacts melanoma cell migration.Highlights.-PFKFB4, a known regulator of glycolysis, displays an unconventional role in melanoma cell migration.-PFKFB4 interacts with ICMT by protein-protein interactions and promotes RAS addressing at the plasma membrane.-PFKFB4 and ICMT cooperation modulates AKT signaling and controls melanoma cell migration.

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Section: Discussionsupporting

confidence: 86%

The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma

Sittewelle

Lécuyer

Monsoro-Burq

2020

Preprint

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“…In many species, the formation of the NC from the unspecified ectoderm relies on the concomitant formation of the adjacent NP, and a specific transcriptome is activated in response to signaling pathways in the early embryo. In frog embryos, this early transcriptome has been described by an EctoMap, which details the spatiotemporal localization of ectoderm specification cascades (Plouhinec et al, 2017; Simoes-Costa, Tan-Cabugao, Antoshechkin, Sauka-Spengler, & Bronner, 2014). Multiple studies have detailed the direct and indirect transcriptional interactions during chicken NC specification and induction, and new details are ever emerging (Prasad, Sauka-Spengler, & LaBonne, 2012; Simoes-Costa & Bronner, 2015; Simoes-Costa, Stone, & Bronner, 2015).…”

Section: | Morphogenesis Tissue Interactions and Nc Inductionmentioning

confidence: 99%

Specifying neural crest cells: From chromatin to morphogens and factors in between

Rogers

Nie

2018

WIREs Developmental Biology

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Neural crest (NC) cells are a stem-like multipotent population of progenitor cells that are present in vertebrate embryos, traveling to various regions in the developing organism. Known as the "fourth germ layer", these cells originate in the ectoderm between the neural plate (NP), which will become the brain and spinal cord, and nonneural tissues that will become the skin and the sensory organs. NC cells can differentiate into more than 30 different derivatives in response to the appropriate signals including, but not limited to, craniofacial bone and cartilage, sensory nerves and ganglia, pigment cells, and connective tissue. The molecular and cellular mechanisms that control the induction and specification of NC cells include epigenetic control, multiple interactive and redundant transcriptional pathways, secreted signaling molecules, and adhesion molecules. NC cells are important not only because they transform into a wide variety of tissue types, but also because their ability to detach from their epithelial neighbors and migrate throughout developing embryos utilizes mechanisms similar to those used by metastatic cancer cells. In this review, we discuss the mechanisms required for the induction and specification of NC cells in various vertebrate species, focusing on the roles of early morphogenesis, cell adhesion, signaling from adjacent tissues, and the massive transcriptional network that controls the formation of these amazing cells. This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Signaling Pathways > Cell Fate Signaling.

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“…59 Protein expression information was queried on Xenbase, 37 EctoMap 1.3, 16 or data available from the primary literature. Gene and protein names are reported following the Xenopus Gene Nomenclature Guidelines (http://www.xenbase.org, RRID: SCR_003280).…”

Section: Methodsmentioning

confidence: 99%

Proteomic Characterization of the Neural Ectoderm Fated Cell Clones in the Xenopus laevis Embryo by High-Resolution Mass Spectrometry

Baxi

Lombard‐Banek

Moody

et al. 2018

ACS Chem. Neurosci.

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The molecular program by which embryonic ectoderm is induced to form neural tissue is essential to understanding normal and impaired development of the central nervous system. Xenopus has been a powerful vertebrate model in which to elucidate this process. However, abundant vitellogenin (yolk) proteins in cells of the early Xenopus embryo interfere with protein detection by high-resolution mass spectrometry (HRMS), the technology of choice for identifying these gene products. Here, we systematically evaluated strategies of bottom-up proteomics to enhance proteomic detection from the neural ectoderm (NE) of X. laevis using nanoflow high-performance liquid chromatography (nanoLC) HRMS. From whole embryos, high-pH fractionation prior to nanoLC-HRMS yielded 1319 protein groups vs 762 proteins without fractionation (control). Compared to 702 proteins from dorsal halves of embryos (control), 1881 proteins were identified after yolk platelets were depleted via sucrose-gradient centrifugation. We combined these approaches to characterize protein expression in the NE of the early embryo. To guide microdissection of the NE tissues from the gastrula (stage 10), their precursor (midline dorsal-animal, or D111) cells were fate-mapped from the 32-cell embryo using a fluorescent lineage tracer. HRMS of the cell clones identified 2363 proteins, including 147 phosphoproteins (without phosphoprotein enrichment), transcription factors, and members from pathways of cellular signaling. In reference to transcriptomic maps of the developing X. laevis, 76 proteins involved in signaling pathways were gene matched to transcripts with known enrichment in the neural plate. Besides a protocol, this work provides qualitative proteomic data on the early developing NE.

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A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates

Cited by 46 publications

References 100 publications

The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma

The glycolysis regulator PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma

Specifying neural crest cells: From chromatin to morphogens and factors in between

Proteomic Characterization of the Neural Ectoderm Fated Cell Clones in the Xenopus laevis Embryo by High-Resolution Mass Spectrometry

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