P-GAP-43 Is Enriched in Horizontal Cell Divisions throughout Rat Cortical Development
1 Center for Molecular Medicine, Department of Developmental Genetics, 1030 Vienna, Austria, 2 Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA, USA and 3 Institute for Stem Cell Research, GSF—National Research Center for Environment and Health, 85764 Neuherberg, Germany and Department of Physiological Genomics, Institute of Physiology, University of Munich, 80633 München, Germany
Address correspondence to Stefan H. Stricker, Center for Molecular Medicine, Dr. Bohrgasse 9/4, 1030 Vienna, Austria. Email: magdalena.goetz{at}gsf.de.
Asymmetric cell divisions are correlated to neurogenesis in the mammalian cortex and occur often with a horizontal orientation of cell division. However, the molecular mechanisms of spindle orientation or asymmetric cell divisions are not well understood in the developing mammalian central nervous system. Here we show a new molecular marker for horizontally dividing precursors in the mammalian telencephalon. The antibody 2G12 directed against phosphorylated serine of growth associated protein 43 (GAP-43) labels postmitotic neurons and a subset of cells in mitoses in the developing rat telencephalon. 2G12 immunoreactivity was found at a high frequency in mitotic cells dividing parallel to the ventricular surface throughout neurogenesis (embryonic day 13–17) in the cerebral cortex and ganglionic eminence. Interestingly, we detected the same predominance of 2G12 immunoreactivity in horizontally dividing cells in the subventricular zone, the second proliferative layer that has recently been involved in the generation of neurons. Moreover, 2G12 immunostaining is no longer detectable in mitotic cells of the ventricular zones at E21, the onset of gliogenesis in rat telencephalon. These data imply GAP-43 phosphorylation in the phase of neuronal commitment during M-phase and present to our knowledge the first molecular correlate to horizontally dividing precursors in mammalian neurogenesis.
Key Words: asymmetric cell division • basal progenitor • GAP-43 • subventricular zone • symmetric cell division • 2G12-immunoreactivity
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