Axon formation is fundamental for brain development and function. TSC1 and TSC2 are two genes, mutations in which cause tuberous sclerosis complex (TSC), a disease characterized by tumor predisposition and neurological abnormalities including epilepsy, mental retardation, and autism. Here we show that Tsc1 and Tsc2 have critical functions in mammalian axon formation and growth. Overexpression of Tsc1/Tsc2 suppresses axon formation, whereas a lack of Tsc1 or Tsc2 function induces ectopic axons in vitro and in the mouse brain. Tsc2 is phosphorylated and inhibited in the axon but not dendrites. Inactivation of Tsc1/Tsc2 promotes axonal growth, at least in part, via up-regulation of neuronal polarity SAD kinase, which is also elevated in cortical tubers of a TSC patient. Our results reveal key roles of TSC1/TSC2 in neuronal polarity, suggest a common pathway regulating polarization/growth in neurons and cell size in other tissues, and have implications for the understanding of the pathogenesis of TSC and associated neurological disorders and for axonal regeneration.[Keywords: Neuronal polarity; tuberous sclerosis complex, TSC; SAD kinase; autism] Supplemental material is available at http://www.genesdev.org.

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The inhibitory effects of the water extract of HangAmDan-B (WEHAD-B), which is a crude extract of eight Korean medicinal animals and plants on bFGF-induced neovascularization were investigated. WEHAD-B significantly prevented bFGF-induced HUVE cell proliferation, adhesion, migration, and capillary-like tubular network formation. Half-maximal inhibition of proliferation on the endothelial cells by WEHAD-B was observed at a concentration of approximately 250 μg/mL. Our antibody microarray-based ProteoChip data showed that WEHAD-B increased the expression of STAT1 and Rb2, which are involved in cell growth, apoptosis, and controlling the cell cycle in bFGF-induced HUVECs. These results indicate that the inhibition of bFGF-induced angiogenesis by WEHAD-B may be due to upregulation of cell signaling proteins, STAT1 and Rb2. The blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD-B was markedly reduced in length compared with a PBS-treated control group. Taken together, these data suggest that antibody-arrayed ProteoChip technology may be an useful tool for determining molecular mechanism of natural products in biological samples.