1. ¹Department of Pathology, St. Mary's Hospital, Kurume, Japan
2. ²Department of Chemistry, Kurume University School of Medicine, Kurume, Japan
3. ³Tissue Engineering Research Center, National Institute of Advanced Industrial Science and Technology, Amagasak, Japan
4. ⁴Department of Neuroanatomy, Osaka University Graduate School of Medicine, Suita, Japan
5. ⁵Institute for Clinical Research, Osaka National Hospital, Chuo-ku, Osaka, Japan
6. ⁶Department of Neurosurgery, Osaka National Hospital, Chuo-ku, Osaka, Japan
7. ⁷Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation (JST), Saitama, Japan
8. ⁸Department of Physiology, Keio University School of Medicine, Tokyo, Japan

Correspondence: Dr. Yasuhiro Nakamura, Department of Pathology, St. Mary's Hospital, 422, Tsubukuhon-machi, Kurume-shi, Japan 830-8543. E-mail: naka@st-mary-med.or.jp

Received 22 January 2003.

Abstract

Recent studies revealed that the "radial glia" in fetal rodent brains are dividing neuronal precursor cells. However, in fetal primate brains, this issue remains unclear, with previous reports indicating that radial glia are a specialized form of astroglia. To investigate the relationship between radial fibers (RFs) and neural stem/progenitor cells in the fetal human brain, we generated polyclonal antibodies to human nestin protein and developed a new mAb, KNY-379, by screening for antibodies that immunostained RFs on paraffin-embedded human fetal brain specimens (12 gestational weeks). The immunostaining for KNY-379 antigen and nestin was seen over the RFs in brains at 8 gestational weeks. Furthermore, KNY-379 antigen and nestin were also detected in human neural stem/progenitor cells in neurosphere cultures. At 12 to 15 gestational weeks, the KNY-379 immunostaining of RFs remained in the periventricular zone and the deep part of the intermediate zone, but it also appeared in outgrowing axons in the cortical plate, in the superficial portion of the intermediate zone, and in apical dendrites in the molecular layer. In the later stages of fetal development (18–40 gestational weeks), this antigen remained in the outgrowing axons and dendrites, but was no longer associated with RFs. Expression cloning and immunoblot analysis demonstrated the antigen to be tubulin beta II, which would thus be a good marker for studying RFs and neural stem/progenitor cells in the early developing human brain.