Regulation of Myelin Synthesis

Lazzarini, R A.

Abstract

The objective of this umbrella project is to acquire a detailed understanding of the developmental program that culminates in myelin synthesis. We are particularly interested in obtaining molecular level information about the control of expression of both the human and murine myelin basic protein (MBP) genes. To this end, we have cDNA cloned and sequenced both the human and mouse MBP genes and studied their organization. During the current reporting period, we have focused on the characterization of the promoter and enhancer regions of the murine MBP. We have made plasmid constructions using these cis-acting elements and a reporter gene whose expression is easily measured. The constructions have been introduced into the germ line of mice so that the tissue specificity of these cis-acting elements can be verified in an in vivo animal model.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Intramural Research (Z01)
• Project #: 1Z01NS002528-08
• Application #: 3922541
• Support Year: 8
• Fiscal Year: 1988

Institution

• Name: National Institute of Neurological Disorders and Stroke
• Country: United States

Publications

Hudson, Lynn D; Romm, Elena; Berndt, Jo Ann et al. (2011) A tool for examining the role of the zinc finger myelin transcription factor 1 (Myt1) in neural development: Myt1 knock-in mice. Transgenic Res 20:951-61

Szuchet, Sara; Nielsen, Joseph A; Lovas, Gabor et al. (2011) The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype. Eur J Neurosci 34:1906-22

Nielsen, Joseph A; Lau, Pierre; Maric, Dragan et al. (2009) Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis. BMC Neurosci 10:98

Lau, Pierre; Verrier, Jonathan D; Nielsen, Joseph A et al. (2008) Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci 28:11720-30

Nielsen, Joseph A; Maric, Dragan; Lau, Pierre et al. (2006) Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling. J Neurosci 26:9881-91

Kim, Hyunsook; Barton, Elisabeth; Muja, Naser et al. (2005) Intact insulin and insulin-like growth factor-I receptor signaling is required for growth hormone effects on skeletal muscle growth and function in vivo. Endocrinology 146:1772-9

Romm, Elena; Nielsen, Joseph A; Kim, Jin G et al. (2005) Myt1 family recruits histone deacetylase to regulate neural transcription. J Neurochem 93:1444-53

Muja, Naser; Lovas, Gabor; Romm, Elena et al. (2004) Expression of a catalytically inactive transmembrane protein tyrosine phosphatase epsilon (tm-PTP epsilon) delays optic nerve myelination. Glia 48:278-97

Nielsen, Joseph A; Berndt, Jo Ann; Hudson, Lynn D et al. (2004) Myelin transcription factor 1 (Myt1) modulates the proliferation and differentiation of oligodendrocyte lineage cells. Mol Cell Neurosci 25:111-23

Hudson, Lynn D (2003) Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin loss from mutations in the same gene. J Child Neurol 18:616-24