Human DCDC2 blocking peptide

Nephronophthisis-related ciliopathies (NPHP-RC) are recessive diseases characterized by renal dysplasia or degeneration. We here identify mutations of DCDC2 as causing a renal-hepatic ciliopathy. DCDC2 localizes to the ciliary axoneme and to mitotic spindle fibers in a cell-cycle-dependent manner. Knockdown of Dcdc2 in IMCD3 cells disrupts ciliogenesis, which is rescued by wild-type (WT) human DCDC2, but not by constructs that reflect human mutations. We show that DCDC2 interacts with DVL and DCDC2 overexpression inhibits beta-catenin-dependent Wnt signaling in an effect additive to Wnt inhibitors. Mutations detected in human NPHP-RC lack these effects. A Wnt inhibitor likewise restores ciliogenesis in 3D IMCD3 cultures, emphasizing the importance of Wnt signaling for renal tubulogenesis. Knockdown of dcdc2 in zebrafish recapitulates NPHP-RC phenotypes, including renal cysts and hydrocephalus, which is rescued by a Wnt inhibitor and by WT, but not by mutant, DCDC2. We thus demonstrate a central role of Wnt signaling in the pathogenesis of NPHP-RC, suggesting an avenue for potential treatment of NPHP-RC.

Dyslexia (reading and spelling disorder) is a very common developmental disorder with a prevalence about 5%. The reading disorder is characterized by a reduced word reading speed, accuracy, and reading comprehension. Reduced orthographic knowledge combined with a high number of spelling errors is characteristic for the spelling disorder. ADHD, depression and dyscalculia are the most common comborbid disorder. Dyslexia often persists into adulthood. Genetic factors are found to be causally related to dyslexia. Based on recent findings on candidate genes and their known functions dyslexia can be regarded as a neuronal migration disorder. Effective treatments are programs that integrate specific approaches of phonological and orthographic awareness trainings and knowledge from learning intervention research.