Lush Mark E, Li Yun, Kwon Chang-Hyuk, Chen Jian, Parada Luis F
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, USA.
J Neurosci. 2008 Feb 13;28(7):1580-7. doi: 10.1523/JNEUROSCI.5236-07.2008.
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.
啮齿动物的桶状皮质是研究基因和神经元活动在神经系统模式形成中作用的有用系统。桶状结构的形成需要几种编码细胞内信号分子或神经递质受体的基因。神经纤维瘤蛋白是一种具有Ras GTP酶活性的肿瘤抑制蛋白,可减弱MAPK(丝裂原活化蛋白激酶)和PI-3激酶(磷脂酰肌醇3激酶)信号通路,在患有1型神经纤维瘤病(NF1)的人类中发生突变。神经纤维瘤蛋白在发育中的和成年的神经系统中广泛表达,NF1的一个常见特征是智力发育缺陷。此外,在自闭症患者中,NF1是一种发病率异常高的疾病。因此,NF1可能在中枢神经系统的正常发育和功能中发挥重要作用。为了探索神经纤维瘤蛋白在中枢神经系统发育中的作用,我们利用了一种小鼠条件性等位基因。我们发现,在大多数皮质神经元和星形胶质细胞中缺乏神经纤维瘤蛋白的小鼠,在躯体感觉皮质中无法形成皮质桶状结构,而丘脑轴突在躯体感觉皮质内的分隔似乎未受影响。