Krox-20 controls myelination in the peripheral nervous system

  title={Krox-20 controls myelination in the peripheral nervous system},
  author={Piotr Topilko and Sylvie Schneider-Maunoury and Giovanni Levi and Anne Baron-Van Evercooren and Amina Ben Younes Chennoufi and Tania Seitanidou and Charles Babinet and Patrick Charnay},
THE molecular mechanisms controlling the process of myelination by Schwann cells remain elusive, despite recent progress in the identification and characterization of genes encoding myelin components (reviewed in ref. 1). We have created a null allele in the mouse Krox-20 gene, which encodes a zinc-finger transcription factor2,3, by in-frame insertion of the Escherichia coli lacZ gene, and have shown that hindbrain segmentation is affected in Krox-20−/− embryos4. We demonstrate here that Krox… 

Peripheral Myelin Maintenance Is a Dynamic Process Requiring Constant Krox20 Expression

It is established that Krox20 is not only required for the onset of myelination but that it is also crucial for the maintenance of the myelinating state, and that myelin maintenance appears as a very dynamic process in which Krox 20 may constitute a molecular switch between Schwann cell myelinations and demyelination programs.

Tead1 regulates the expression of Peripheral Myelin Protein 22 during Schwann cell development.

While Pmp22 enhancers marked by active histone modifications were lost or remodeled after injury, it was found that these enhancers were permissive in early development prior to PMP22 upregulation, identifying Tead1 as a novel regulator of Pmp 22 expression during development in concert with Sox10 and Egr2.

New insights into signaling during myelination in zebrafish.

Uncoupling of Myelin Assembly and Schwann Cell Differentiation by Transgenic Overexpression of Peripheral Myelin Protein 22

It is suggested that PMP22, when overexpressed, accumulates in a late Golgi–cell membrane compartment and uncouples myelin assembly from the underlying program of Schwann cell differentiation.

Dicer in Schwann Cells Is Required for Myelination and Axonal Integrity

The data indicate that miRNAs critically regulate Schwann cell gene expression that is required for myelination and to maintain axons via axon–glia interactions.

Cthrc1 is a negative regulator of myelination in schwann cells

It is established that CthRC1 enhances Schwann cell proliferation but prevents myelination, and time‐course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin Formation with cells maintaining a proliferative state.

The regulation of Krox-20 expression reveals important steps in the control of peripheral glial cell development.

The regulation of Krox-20 expression in peripheral glial cells reveals three important steps in the development and differentiation of Schwann cells, which appears to be a key component of the transduction cascade linking axonal signalling to myelination.

Profilin 1 is required for peripheral nervous system myelination

It is shown that SC lamellipodia formation depends on the function of profilin 1 (Pfn1), an actin-binding protein involved in microfilament polymerization, and this protein is identified as a key effector of the integrin linked kinase/Rho/ROCK pathway.

Establishment of myelinating schwann cells and barrier integrity between central and peripheral nervous systems depend on Sox10

It is inferred that in addition to its many roles in Schwann cells, Sox10 is also important for the integrity of the boundary between central and peripheral nervous systems.

Control of myelination in Schwann cells: a Krox20 cis‐regulatory element integrates Oct6, Brn2 and Sox10 activities

The results resolve previous controversy concerning the mechanism of action of Oct6 and Brn2 during myelination and provide an explanation for myelin deficiencies in Waardenberg–Hirschsprung disease patients whereby Sox10 mutations could lead to a loss of Krox20 expression.



The molecular genetics of myelination: An update

The PMP22/gas3 gene has been found to encode an axonally regulated Schwann cell protein that is assembled into PNS myelin, and appears to be the target of mutations that result in the Trembler alleles in mice, and in Charcot‐Marie‐Tooth disease Type 1a.

Compact myelin exists in the absence of basic protein in the shiverer mutant mouse

The shiverer mouse is unique in showing a striking alteration in myelin protein composition that does not significantly affect the gross morphology and lamellar organisation of the myelin sheath, and this results question the proposed role of basic proteins15–19 in Myelin as ‘structural cement’.

Myelination in the absence of myelin-associated glycoprotein

It is indicated that MAG is necessary for maintenance of the cytoplasmic collar and periaxonal space of myelinated fibres and not critical for myelin formation.

Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse

The demonstration that neuromeres are domains of gene expression provides molecular evidence for the segmentation of the CNS.

Distribution of the myelin-associated glycoprotein and P0 protein during myelin compaction in quaking mouse peripheral nerve

  • B. Trapp
  • Biology, Chemistry
    The Journal of cell biology
  • 1988
The results indicated that conversion of mesaxon membranes to compact myelin involves the insertion of P0 protein into and the removal of the myelin-associated glycoprotein from mesXon membranes.

Immunocytochemical studies of quaking mice support a role for the myelin-associated glycoprotein in forming and maintaining the periaxonal space and periaxonal cytoplasmic collar of myelinating Schwann cells

The immunocytochemical localization of MAG is determined in the L4 ventral roots from 11-mo-old quaking mice and it is hypothesized that MAG plays a structural role in forming and maintaining contact between myelinating Schwann cells and the axon and maintaining the Schwann cell periaxonal cytoplasmic collar of myelinated fibers.

Schwann cells depleted of galactocerebroside express myelin‐associated glycoprotein and initiate but do not continue the process of myelination

Two peripheral myelin components, galactocerebroside (GalC) and myelin‐associated glycoprotein (MAG), are known to be expressed early in Schwann cell differentiation, prior to the formation of

Presence of the myelin-associated glycoprotein correlates with alterations in the periodicity of peripheral myelin

It is proposed that MAG plays a role in maintaining the periaxonal space, Schmidt-Lantermann incisures, paranodal myelin loops, and outer mesaxon by preventing "complete" compaction of Schwann cell and myelin membranes.