28 research outputs found
Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice
As revealed in a new model of cerebral cavernous malformations (CCM), the timing of ablation of Ccm genes determines whether or not CCM lesions arise in brain and retina venous beds
PDCD10/CCM3 Acts Downstream of Îł-Protocadherins to Regulate Neuronal Survival*
Îł-Protocadherins (PCDH-Îł) regulate neuronal survival in the vertebrate central nervous system. The molecular mechanisms of how PCDH-Îł mediates this function are still not understood. In this study, we show that through their common cytoplasmic domain, different PCDH-Îł isoforms interact with an intracellular adaptor protein named PDCD10 (programmed cell death 10). PDCD10 is also known as CCM3, a causative genetic defect for cerebral cavernous malformations in humans. Using RNAi-mediated knockdown, we demonstrate that PDCD10 is required for the occurrence of apoptosis upon PCDH-Îł depletion in developing chicken spinal neurons. Moreover, overexpression of PDCD10 is sufficient to induce neuronal apoptosis. Taken together, our data reveal a novel function for PDCD10/CCM3, acting as a critical regulator of neuronal survival during development