CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure

Cherie Southwood; Chris He; James Garbern; John Kamholz; Edgardo Arroyo; Alexander Gow

doi:10.1523/JNEUROSCI.3479-04.2004

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CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure

Journal article

Open access

Peer reviewed

CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure

Cherie Southwood, Chris He, James Garbern, John Kamholz, Edgardo Arroyo and Alexander Gow

The Journal of neuroscience, Vol.24(50), pp.11215-11225

12/15/2004

DOI: 10.1523/JNEUROSCI.3479-04.2004

PMCID: PMC6730372

PMID: 15601927

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Abstract

Homeodomain proteins play critical roles during development in cell fate determination and proliferation, but few studies have defined gene regulatory networks for this class of transcription factors in differentiated cells. Using a lacZ-knock-in strategy to ablate Nkx6-2, we find that the Nkx6-2 promoter is active embryonically in neuroblasts and postnatally in oligodendrocytes. In addition to neurological deficits, we find widespread ultrastructural abnormalities in CNS white matter and aberrant expression of three genes encoding a paranodal microtubule destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules neurofascin and contactin. The involvement of these downstream proteins in cytoskeletal function and cell adhesion reveals mechanisms whereby Nkx6-2 directly or indirectly regulates axon- glial interactions at myelin paranodes. Nkx6-2 does not appear to be the central regulator of axoglial junction assembly; nonetheless, our data constitute the first evidence of such a regulatory network and provide novel insights into the mechanism and effector molecules that are involved.

Oligodendroglia - metabolism

Central Nervous System - metabolism

Phosphoproteins - metabolism

Psychomotor Performance - physiology

Recombinant Fusion Proteins

Central Nervous System - physiology

Central Nervous System - anatomy & histology

Gene Expression Regulation, Developmental

Nerve Tissue Proteins - biosynthesis

Cranial Nerves - embryology

Myelin Sheath - physiology

Nerve Tissue Proteins - physiology

Transcription Factors - physiology

Homeodomain Proteins - biosynthesis

Cranial Nerves - metabolism

Microtubule Proteins - metabolism

Transcription Factors - biosynthesis

Mice, Knockout

Motor Neurons - metabolism

Stathmin

Rotarod Performance Test

Transcription, Genetic - physiology

Animals

Intercellular Junctions - physiology

Mice

Myelin Sheath - ultrastructure

Homeodomain Proteins - physiology

Intercellular Junctions - ultrastructure

Evoked Potentials, Auditory, Brain Stem - physiology

Details

Title: Subtitle: CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure
Creators: Cherie Southwood - Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York, 10029, USA
Chris He
James Garbern
John Kamholz
Edgardo Arroyo
Alexander Gow
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.24(50), pp.11215-11225
Publisher: United States
DOI: 10.1523/JNEUROSCI.3479-04.2004
PMID: 15601927
PMCID: PMC6730372
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: R01 DC006262 / NIDCD NIH HHS DC006262 / NIDCD NIH HHS
Language: English
Date published: 12/15/2004
Academic Unit: Neurology; Psychiatry
Record Identifier: 9984020646502771

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