Development of the human insular cortex: differentiation, proliferation, cell death, and appearance of 5HT-2A receptors

The development of the human insula was studied in the foetuses from 21 to 32 gestation weeks, using silver staining, immunohistochemistry of proliferative cell nuclear antigen (PCNA), activated caspase-3, and TdT-mediated dUTP-biotin nick end labeling (TUNEL) techniques. To test whether the insula also has a significant role in psychiatry behavior, we also mapped the major receptor of serotonin, 5HT-2A, in the developing insula as well. Opercular formation was evident by 21 weeks gestation. At this time, the cortical layers in the insula had started to organize, with silver impregnated pyramidal and stellate cells demonstrated various processes. By 25 gestation weeks, gyri in the insula were observed. PCNA positive cells decreased in density from 21 gestation weeks onwards while an increase of TUNEL positive cells was evident from 25 to 32 weeks of gestation. Activated capase-3 positive cells were detected in the insula, along with TUNEL positive cells, confirming possibly apoptosis. Serotonin 2A receptor appeared robustly in the 31/32 gestation week specimens. Our study showed early differentiation in the insula, when compared with other parts of the human cortex in the literature. In addition, proliferation as well as apoptosis were demonstration. Expression of 5HT (serotonin) 2A receptor positive cells in development was indicative of the insula as a signiWcant psychiatric center.