TIEN-CHENG WANG, YI-HSUAN LI, KUAN-WEI CHEN, CHING-JEN CHEN, CHIA-LING WU, NAN-YUAN TENG, AND LINYI CHEN 2063 SH2B1 Regulates N-Cadherin Published online in Wileyonlinelibrary, 6 December 2010 The interplay between cell-cell and cell-extracellular matrix adhesion contributes to cell fate determination during development. The cell adhesion molecule N-cadherin mediates cell-cell adhesion and regulates cell motility in various systems. Wang et al. demonstrate that overexpression of the signaling adaptor protein SH2B1β reduces, while the dominant negative mutant of SH2B1β increases, the expression of N-cadherin in PC12 cells, a well-established neuronal model system. Through binding to N-cadherin, SH2B1β may recruit a putative kinase to phosphorylate β-catenin, reduce N-cadherin-β-catenin complexes and thus the inter-cellular interaction. In the presence of nerve growth factor (NGF), SH2B1β leaves the N-cadherin-containing complexes, allowing N-cadherin to accumulate at the cell surface during neurite elongation. Results from this study implicate the differential requirement of N-cadherin during neurite initiation and elongation which is challenging to address using primary neural culture or in vivo systems. Wang et al. present a novel mechanism by which the adaptor protein SH2B1β reduces N-cadherin levels and cell-cell adhesion to promote earlier neurite initiation. This mechanism also explains why overexpression of the dominant negative mutant SH2B1β(R555E) blocks neurite initiation without inhibiting NGF signaling. B. D’ANGELO, E. BENEDETTI, S. DI LORETO, L. CRISTIANO, G. LAURENTI, M.P. CERÙ, AND A. CIMINI 2170 PPAR/-Induced Neuronal Differentiation Published online in Wileyonlinelibrary, 6 December 2010 A fundamental problem in neuroblastomas is the high mortality rate and rapid tumor progression. In particular, pediatric patients whose neuroblastomas express high levels of BDNF and TrkB have an unfavourable prognosis. PPARβ/δ is a transcription factor abundantly expressed in the central nervous system, and was recently impli- cated in neuronal differentiation. D’Angelo et al. demonstrate that PPARβ/δ natural and synthetic ligands trigger neuronal differentiating activity in neuroblastoma cells. This effect relates to their ability to modulate BDNF and TrkB expression. This leads to a decrease in cell proliferation, neuronal differentiation and an increase of neuronal differentiation markers, thus suggesting a new therapeutic strategy for neuroblas- toma. The authors also investigated neuroblastoma cells after PPAR β/δ silencing and the effects of natural and synthetic PPARβ/δ ligands on the BDNF signal transduction pathway. After silencing, no differentiating activity was observed, thus supporting PPARβ/δ’s dependence on differentiating effects. The authors provide evidence to further support the important role of PPAR β/δ as a modulator of pathways crucial for neuronal differentiation. VOL. 226 AUGUST 2011 NO. 8 HIGHLIGHTS vi page 2073 page 2178