Ratner Lab
Oligodendrocyte Development and Myelin Defects in Rasopathy Mutants

Oligodendrocyte Development and Myelin Defects in Rasopathy Mutants

Oligodendrocytes myelinate axons in the CNS, providing an increased conductivity for the electrical nerve impulses traveling through the axons. Some of the non-tumor problems of NF1 patients, such as learning disabilities, hydrocephaly and T2 hyper-intensities identified by MRIs (thought to represent areas of abnormal-myelin), led us to study oligodendrocyte development and function in NF1 mouse models. Examining how oligodendrocytes are altered may provide potential therapeutic avenues.

Related Publications

Titus HE, López-Juárez A, Silbak SH, Rizvi TA, Bogard M, Ratner N. Oligodendrocyte RasG12V expressed in its endogenous locus disrupts myelin structure through increased MAPK, nitric oxide, and notch signaling. Glia. 2017 Dec;65(12):1990-2002.

López-Juárez A, Titus HE, Silbak SH, Pressler JW, Rizvi TA, Bogard M, Bennett MR, Ciraolo G2, Williams MT, Vorhees CV, Ratner N. Oligodendrocyte Nf1 Controls Aberrant Notch Activation and Regulates Myelin Structure and Behavior. Cell Rep. 2017 Apr 18;19(3):545-557.

Mayes DA, Rizvi TA, Titus-Mitchell H, Oberst R, Ciraolo GM, Vorhees CV, Robinson AP, Miller SD, Cancelas JA, Stemmer-Rachamimov AO, Ratner N. Nf1 loss and Ras hyperactivation in oligodendrocytes induce NOS-driven defects in myelin and vasculature. Cell Rep. 2013 Sep 26;4(6):1197-212.

Bennett MR, Rizvi TA, Karyala S, McKinnon RD, Ratner N. Aberrant growth and differentiation of oligodendrocyte progenitors in neurofibromatosis type 1 mutants. J Neurosci. 2003 Aug 6;23(18):7207-17.

Rizvi TA, Akunuru S, de Courten-Myers G, Switzer RC 3rd, Nordlund ML, Ratner N. Region-specific astrogliosis in brains of mice heterozygous for mutations in the neurofibromatosis type 1 (Nf1) tumor suppressor. Brain Res. 1999 Jan 16;816(1):111-23.

Daston MM, Scrable H, Nordlund M, Sturbaum AK, Nissen LM, Ratner N. The protein product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes. Neuron. 1992 Mar;8(3):415-28.

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For more information about the lab, contact Nancy Ratner, PhD, at  513-636-9469. 
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