The Lin28/let-7 axis is critical for myelination in the peripheral nervous system

Gökbuget, Deniz; Pereira, Jorge A.; Bachofner, Sven; Marchais, Antonin; Ciaudo, Constance; Stoffel, Markus; Schulte, Johannes H.; Suter, Ueli

doi:10.1038/ncomms9584

Cited by 40 publications

(39 citation statements)

References 43 publications

(50 reference statements)

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“…To assess similarities and differences in the requirement of miRNA biogenesis pathway components Drosha, Dgcr8, and Dicer in developing SCs quantitatively and in parallel, we generated conditional SC‐specific loss‐of‐function mice ( Mus musculus ) for Dicer (Dicer cKO), Dgcr8 (Dgcr8 cKO), and Drosha (Drosha cKO) using a previously established Cre recombinase system expressed under Dhh gene regulatory sequences (Figure a) (Jaegle et al, ). As expected, the levels of Dicer, Dgcr8, and Drosha mRNAs and SN‐enriched miRNAs (Gökbuget et al, ) were strongly diminished in respective mutant mice at postnatal day (P) 1 (Figure b–e). Morphological analysis of SNs at P24 revealed numerous aberrant large bundles of unsorted axons, usually a unique feature of SC differentiation during the early stage of radial sorting, specifically in Dgcr8 cKO and Drosha cKO (Figure f–i).…”

Section: Resultssupporting

confidence: 73%

“…The long RNA sequencing data have been deposited at the NCBI GEO database with the primary accession code GSE109075. The long RNA sequencing data for conditional Dicer mutants and controls was retrieved from the dataset available at the NCBI GEO database (GSE64562) (Gökbuget et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…We have recently found that let‐7 miRNAs drive the onset of myelination (Gökbuget et al, ), and loss of Dgcr8 or Dicer in SCs impaired this developmental process (Bremer et al, ; Lin, Oksuz, Hurley, Wrabetz, & Awatramani, ; Pereira et al, ; Verrier, Semple‐Rowland, Madorsky, Papin, & Notterpek, ; Yun et al, ). Dgcr8‐ablated SCs appeared to be more affected than Dicer‐ablated SCs, in line with potential additional functions of the microprocessor in myelination (Lin et al, ).…”

Section: Introductionmentioning

confidence: 99%

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The miRNA biogenesis pathway prevents inappropriate expression of injury response genes in developing and adult Schwann cells

Gökbuget

Pereira

Opitz

et al. 2018

Glia

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Proper function of the nervous system depends on myelination. In peripheral nerves, Schwann cells (SCs) myelinate axons and the miRNA biogenesis pathway is required for developmental myelination and myelin maintenance. However, regulatory roles of this pathway at different stages of myelination are only partially understood. We addressed the requirement of the core miRNA biogenesis pathway components Dgcr8, Drosha, and Dicer in developing and adult SCs using mouse mutants with a comparative genetics and transcriptomics approach. We found that the microprocessor components Dgcr8 and Drosha are crucial for axonal radial sorting and to establish correct SC numbers upon myelination. Transcriptome analyses revealed a requirement of the microprocessor to prevent aberrantly increased expression of injury‐response genes. Those genes are predicted targets of abundant miRNAs in sciatic nerves (SNs) during developmental myelination. In agreement, Dgcr8 and Dicer are required for proper maintenance of the myelinated SC state, where abundant miRNAs in adult SNs are predicted to target injury‐response genes. We conclude that the miRNA biogenesis pathway in SCs is crucial for preventing inappropriate activity of injury‐response genes in developing and adult SCs.

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Section: Resultssupporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The miRNA biogenesis pathway prevents inappropriate expression of injury response genes in developing and adult Schwann cells

Gökbuget

Pereira

Opitz

et al. 2018

Glia

Self Cite

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“…3A). A recent study has revealed that peripheral nerve KROX20 induction is regulated by the Lin28/Let-7 axis (Gokbuget et al 2015). Lin28 is a conserved RNA-binding protein that is expressed highly in embryonic stem cells.…”

Section: Bcl2mentioning

confidence: 99%

Identification of hair shaft progenitors that create a niche for hair pigmentation

et al. 2017

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Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20 + cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes.

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“…Let-7 promotes expression of the myelination-driving master transcription factor Krox20 (also known as Egr2) through suppression of myelination inhibitory Notch signaling. As let-7 is also highly expressed in CNS, it remains unknown if let-7 is also responsible for CNS myelinations [80]. …”

Section: Micrornas and Extrinsic Determinants Of Axon Regenerationmentioning

confidence: 99%

Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

Teng

Liu

2016

Neural Plasticity

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Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes' expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord.

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The Lin28/let-7 axis is critical for myelination in the peripheral nervous system

Cited by 40 publications

References 43 publications

The miRNA biogenesis pathway prevents inappropriate expression of injury response genes in developing and adult Schwann cells

The miRNA biogenesis pathway prevents inappropriate expression of injury response genes in developing and adult Schwann cells

Identification of hair shaft progenitors that create a niche for hair pigmentation

Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

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