Sonic hedgehog functions upstream of disrupted-in-schizophrenia 1 (disc1): implications for mental illness.

摘要: DISRUPTED-IN-SCHIZOPHRENIA (DISC1) has been one of the most intensively studied genetic risk factors for mental illness since it was discovered through positional mapping a translocation breakpoint in large Scottish family where balanced chromosomal found to segregate with schizophrenia and affective disorders. While evidence being central disease pathogenesis original is compelling, recent genome-wide association studies have not common variants at DISC1 locus associated wider population. It may therefore be case that provides an indication biological pathways are health issues functional shown functions multiple signalling pathways. However, there little information regarding function upstream regulate its expression function. We herein demonstrate Sonic hedgehog (Shh) promotes disc1 zebrafish brain. Expression lost smoothened mutants complete loss Shh signal transduction, elevated patched which constitutive activation signalling. previously demonstrated knockdown dramatic effect on specification oligodendrocyte precursor cells (OPC) hindbrain known essential these cells. show prominently expressed olig2-positive midline progenitor absent smo mutants, while cyclopamine treatment blocks mimics knock down OPC specification. Various features number psychiatric conditions could potentially arise aberrant Hedgehog suggest altered important neurodevelopmental factor pathobiology illness.