Sensitive phases for teratogen-induced developmental defects in the brain

Developmental stage-dependent susceptibility to teratogens and sensitive period can be regarded as one of the essential points which characterize teratogenesis. In this paper, emphasis is given to a review of our studies on the critical developmental stage for induction of histogenetic disorders of the cerebral cortex and on the high vulnerability of developing neural cells to teratogenic agents. The undifferentiated ventricular cells in the mammalian fetal telencephalon are particularly vulnerable to various cytotoxic agents at the time when the ventricular cells start to differentiate into cerebral cortical neurons and the cortical plate appears. This period is day 13 of gestation in mice, day 15 in rats and 8 weeks after fertilization in humans. This developmental stage of the brain corresponds to the period of highest sensitivity for induction of cerebral cortical disorders observed postnatally both in laboratory animals and in humans. One of the significant factors determining the period of highest sensitivity of the ventricular cells could be a certain initial phase of cytodifferentiation in G1 and G0 phase cells prior to their actual morphological differentiation.