Demarcation of early mammalian cortical development by differential expression of fringe genes

Fringe has originally been found in Drosophila as a gene encoding a putativ e secreted protein which regulates the sensitivity of Notch signaling pathw ay to different ligands. We show that three members of murine fringe gene f amily, Lunatic fringe (L-fng), Manic fringe (M-fng) and Radical fringe (R-f ng), show related patterns of expression in the developing cerebral wall. L -fng is expressed in immature cells in the ventricular zone. M-fng is upreg ulated transiently in maturing neurons when they leave the ventricular zone (VZ). R-fng is upregulated in more mature neurons when they enter the prep late and cortical plate. These patterns suggest that the transition from im mature to mature neurons involves sequential changes in the member of fring e family genes expressed. More detailed expression analyses of fringe genes and immunohistochemistry for neuron-specific class III beta-tubulin sugges t a mode of neurogenesis which might underlie the histogenesis of the cereb ral cortex. A proliferative population situated outside of the VZ is define d as M-fng-positive/BrdU-positive cells, which constitutes about 10-20% of the total S-phase cells in the cerebral wall of embryonic day 10.5-12.5. We found that M-fng is expressed in mitotic figures outside the VZ and some o f them react with the antibody against class III P-tubulin. These observati ons suggest that a significant number of proliferative cells exist outside the VZ, which supply neurons during early cortical development. (C) 2000 El sevier Science B.V. All rights reserved.