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The Journal of Neuroscience, February 13, 2008, 28(7):1580-1587; doi:10.1523/JNEUROSCI.5236-07.2008

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Development/Plasticity/Repair
Neurofibromin Is Required for Barrel Formation in the Mouse Somatosensory Cortex

Mark E. Lush, * Yun Li, * Chang-Hyuk Kwon, Jian Chen, and Luis F. Parada

Department of Developmental Biology and Kent Waldrep Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133

Correspondence should be addressed to Dr. Luis F. Parada at the above address. Email: luis.parada{at}utsouthwestern.edu

The rodent barrel cortex is a useful system to study the role of genes and neuronal activity in the patterning of the nervous system. Several genes encoding either intracellular signaling molecules or neurotransmitter receptors are required for barrel formation. Neurofibromin is a tumor suppressor protein that has Ras GTPase activity, thus attenuating the MAPK (mitogen-activated protein kinase) and and PI-3 kinase (phosphatidylinositol 3-kinase) pathways, and is mutated in humans with the condition neurofibromatosis type 1 (NF1). Neurofibromin is widely expressed in the developing and adult nervous system, and a common feature of NF1 is deficits in intellectual development. In addition, NF1 is an uncommonly high disorder among individuals with autism. Thus, NF1 may have important roles in normal CNS development and function. To explore roles for neurofibromin in the development of the CNS, we took advantage of a mouse conditional allele. We show that mice that lack neurofibromin in the majority of cortical neurons and astrocytes fail to form cortical barrels in the somatosensory cortex, whereas segregation of thalamic axons within the somatosensory cortex appears unaffected.

Key words: NF1; Ras-GAP; hGFAP-Cre; thalamocortical axons; development; conditional mutant

Received Sept. 22, 2006; accepted Dec. 26, 2007.

Correspondence should be addressed to Dr. Luis F. Parada at the above address. Email: luis.parada{at}utsouthwestern.edu


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