Characterisation of<i>cis</i>-acting sequences reveals a biphasic, axon-dependent regulation of<i>Krox20</i>during Schwann cell development

Ghislain, Julien; Desmarquet-Trin-Dinh, Carole; Jaegle, Martine; Meijer, Dies; Charnay, Patrick; Frain, Monique

doi:10.1242/dev.129.1.155

Cited by 68 publications

(10 citation statements)

References 48 publications

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“…POU Domain Transcription Factors. Oct-6 is a POU domain transcription factor that controls Krox-20 expression (Blanchard et al, 1996;Ghislain et al, 2002). During mammalian development, Oct-6 is transiently expressed in promyelinating SCs, with highest expression during the transition to myelinating SCs.…”

Section: Signaling Pathways Activated In Schwann Cell Myelinationmentioning

confidence: 99%

New insights on schwann cell development

Monk

Feltri

Taveggia

2015

Glia

225

218

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In the peripheral nervous system, Schwann cells are glial cells that are in intimate contact with axons throughout development. Schwann cells generate the insulating myelin sheath and provide vital trophic support to the neurons that they ensheathe. Schwann cell precursors arise from neural crest progenitor cells, and a highly ordered developmental sequence controls the progression of these cells to become mature myelinating or non-myelinating Schwann cells. Here, we discuss both seminal discoveries and recent advances in our understanding of the molecular mechanisms that drive Schwann cell development and myelination with a focus on cell-cell and cell-matrix signaling events.

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Section: Signaling Pathways Activated In Schwann Cell Myelinationmentioning

confidence: 99%

New insights on schwann cell development

Monk

Feltri

Taveggia

2015

Glia

225

218

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“…As mentioned earlier, the zinc finger transcription factor Krox20/Egr2 is a major target of Oct6/Brn2 regulation. Activation of Krox20/Egr2 transcription in Schwann cells is mediated through a cis-acting element in the Krox20/Egr2 locus called the myelin-associated Schwann cell enhancer or mSCE (Ghislain and Charnay, 2006;Ghislain et al, 2002). Cotransfection experiments have shown that Oct6/Scip, Brn2, and Sox10 synergistically activate a reporter through this enhancer (Ghislain and Charnay, 2006;Kuhlbrodt et al, 1998a).…”

Section: Feed-forward Coordination Of Commitment To Myelinationmentioning

confidence: 99%

The molecular machinery of myelin gene transcription in Schwann cells

Svaren

Meijer

2008

Glia

Self Cite

218

209

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During late fetal life, Schwann cells in the peripheral nerves singled out by the larger axons will transit through a promyelinating stage before exiting the cell cycle and initiating myelin formation. A network of extra-and intracellular signaling pathways, regulating a transcriptional program of cell differentiation, governs this progression of cellular changes, culminating in a highly differentiated cell. In this review, we focus on the roles of a number of transcription factors not only in myelination, during normal development, but also in demyelination, following nerve trauma. These factors include specification factors involved in early development of Schwann cells from neural crest (Sox10) as well as factors specifically required for transitions into the promyelinating and myelinating stages (Oct6/ Scip and Krox20/Egr2). From this description, we can glean the first, still very incomplete, contours of a gene regulatory network that governs myelination and demyelination during development and regeneration. V V C 2008 Wiley-Liss, Inc. TRANSCRIPTIONAL CONTROL OF MYELINATION AND DEMYELINATIONMyelination promoting signals (discussed in other reviews in this special issue of Glia) converge on a number of transcription factors to drive the transition of immature, promyelinating proliferative cells to myelinating cells. Over the last decade, several transcription factors were found to play key roles in this transition and the execution of a transcriptional program directing myelination. These transcription factors, their regulatory relationships, and the intracellular signaling pathways that modulate their activity have been studied with growing intensity over the last few years. These studies have revealed a number of regulatory circuits that outline the contours of a gene regulatory network of myelination in the peripheral nervous system. A simplified outline of this network is depicted in Fig. 1. A myelination promoting circuit, consisting of the POU domain factors Oct6/Scip, Brn2, and Sox10 that regulate Krox20/Egr2 and drives the promyelinating to myelinating transition, forms the backbone of this regulatory network. More recently, a second cross-antagonistic circuit of Krox20/Egr2 versus cJun and Sox2 has been described that governs active demyelination following nerve trauma. In the following sections, we will discuss the different transcription factors, their mechanism of action, and their regulatory relationships.

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“…Sox10 is expressed throughout all stages of Schwann cell development and is necessary for embryonic and mature Schwann cell differentiation (20,(22)(23)(24)(25). In promyelinating cells, Sox10 upregulates expression of Egr2 (26)(27)(28)(29). Egr2 is required for myelination and myelin maintenance, and activates a number of myelin-associated genes (21,30,31).…”

Section: Introductionmentioning

confidence: 99%

Tead1 regulates the expression ofPeripheral Myelin Protein 22during Schwann cell development

Lopez‐Anido¹,

Poitelon

Gopinath

et al. 2016

Hum. Mol. Genet.

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Schwann cells are myelinating glia in the peripheral nervous system that form the myelin sheath. A major cause of peripheral neuropathy is a copy number variant involving the Peripheral Myelin Protein 22 (PMP22) gene, which is located within a 1.4-Mb duplication on chromosome 17 associated with the most common form of Charcot-Marie-Tooth Disease (CMT1A). Rodent models of CMT1A have been used to show that reducing Pmp22 overexpression mitigates several aspects of a CMT1A-related phenotype. Mechanistic studies of Pmp22 regulation identified enhancers regulated by the Sox10 (SRY sex determining region Y-box 10) and Egr2/Krox20 (Early growth response protein 2) transcription factors in myelinated nerves. However, relatively little is known regarding how other transcription factors induce Pmp22 expression during Schwann cell development and myelination. Here, we examined Pmp22 enhancers as a function of cell type-specificity, nerve injury and development. While Pmp22 enhancers marked by active histone modifications were lost or remodeled after injury, we found that these enhancers were permissive in early development prior to Pmp22 upregulation. Pmp22 enhancers contain binding motifs for TEA domain (Tead) transcription factors of the Hippo signaling pathway. We discovered that Tead1 and co-activators Yap and Taz are required for Pmp22 expression, as well as for the expression of Egr2 Tead1 directly binds Pmp22 and Egr2 enhancers early in development and Tead1 binding is induced during myelination, correlating with Pmp22 expression. The data identify Tead1 as a novel regulator of Pmp22 expression during development in concert with Sox10 and Egr2.

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Characterisation ofcis-acting sequences reveals a biphasic, axon-dependent regulation ofKrox20during Schwann cell development

Cited by 68 publications

References 48 publications

New insights on schwann cell development

New insights on schwann cell development

The molecular machinery of myelin gene transcription in Schwann cells

Tead1 regulates the expression ofPeripheral Myelin Protein 22during Schwann cell development

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