APOPTOSIS AND BCL-2 ONCOPROTEIN EXPRESSION IN THE HUMAN FETAL CENTRAL-NERVOUS-SYSTEM

Apoptosis and the apoptosis-regulatory gene bcl-2 have been suggested from animal studies to be important during the development of the cent ral nervous system (CNS), but information on apoptotic activities of t he developing human CNS has been scarce. To establish spatial and temp oral distributions of apoptotic cells and Bcl-2 oncoprotein expression , we examined sections taken fi om cerebral cortex, hippocampus and br ainstem at weeks 14, 18, 27, and 32 of gestation. Terminal transferase -mediated nick end labelling (TUNEL), histological analyses, and immun ocytochemical staining using monoclonal antibodies were employed. Exce pt for layer I of the motor cortex and the molecular layer of the hipp ocampus, both at week 14 of gestation, TUNEL-positive cells with typic al apoptotic appearance and apoptotic indices, ranging from 0.08 to 2. 85, were found in all other brain regions examined including visual, s ensory, frontal and motor cortices, hippocampus, dorsal raphe, locus c oeruleus, and periaqueductal grey of the brainstem. No specific spatia l or temporal distribution patterns of apoptotic cells were found in t he cortices. However, the apoptotic index of the molecular layer of th e hippocampus increased with the gestation age. The periaqueductal gre y of the brainstem showed high apoptotic indices (ranging from 0.37 to 2.85) at all the gestation ages studied. An inverse correlation betwe en apoptosis and Bcl-2 oncoprotein expression was found in visual, sen sory and motor cortices but not in the frontal cortex and hippocampus. Apoptosis and Bcl-2 oncoproteins are important for CNS development an d, apart from being an apoptosis regulator, Bcl-2 oncoproteins may als o have other roles to play during neural development. Anat. Rec. 252:1 65-175, 1998. (C) 1998 Wiley-Liss, Inc.