Development of astrocytes in the mouse embryonic cerebrum tracked by tenascin-C gene expression.

Abstract

The development of astrocytes in the rodent cerebrum has been considered to occur mainly in the perinatal stage after the end of neurogenesis, and the mode of generation and migration of the astroglial precursors in the embryonic cerebrum remains poorly understood. Tenascin-C (TN-C) is an astroglia-derived extracellular matrix molecule, and its expression can be traced to the ventricular germinative zone of the embryonic cerebrum. TN-C expression may therefore be used as a marker of astroglial precursors prior to the expression of the glial fibrillary acidic protein (GFAP), a marker for the late stage of astroglial differentiation. The development of astrocytes in the mouse embryonic cerebrum was examined by in situ hybridization histochemistry for TN-C mRNA as an early marker. Observations showed that TN-C-positive cells were aligned in the ventricular germinative zone and began to migrate radially at E (embryonic day) 15. They were dispersed into the cortex as early as E17, and some were still in the DNA synthetic phase (S phase) even after lodgement in the cortex. TN-C-positive cells differentiated into GFAP-immunopositive astrocytes in the cortical and subcortical areas at the neonatal stage. The distribution of their active generation sites in the ventricular germinative zone was not homogeneous but displayed a restricted pattern. The mode of their migration towards the cortical and subcortical areas also showed a characteristic pattern that correlated to the radial glial arrangement. These findings indicate that TN-C-positive cells represent a new subset of astroglial precursors which arise directly from the ventricular germinative zone, and that astrogliogenesis from this precursor occurs as early as the period of neurogenesis at the embryonic stage.