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Published February 1, 1995 | Published
Journal Article Open

FORSE-1: A Positionally Regulated Epitope in the Developing Rat Central Nervous System

Abstract

We designed a protocol to identify cell surface molecules expressed in restricted spatial patterns in the developing central nervous system (CNS) that might be regulated by regionally restricted transcription factors. The immunogen was a membrane fraction from NT2/D1 embryocarcinoma cells that were induced to differentiate into neurons and upregulate Hox gene expression in response to retinoic acid. One monoclonal antibody (mAb), FORSE-1, specifically labels the rostral rat CNS from the earliest stages. Staining is observed in the rostral but not caudal neural folds of the embryo prior to neural tube closure. Staining is enriched in the forebrain as compared to the rest of the CNS, until E18. Between E11.5 and E13.5, only certain areas of the telencephalon and diencephalon are labeled. Later, up to E17.5, FORSE-1 labeling is specifically restricted to the telencephalon, where a correlation with mitotic activity is apparent: the ventricular zone labels with FORSE-1, while the cortical plate is negative. The staining of the neuroepithelium is intensified by acetone fixation, which also reveals, between E11.5 and E13.5, a dorsoventrally restricted, FORSE-1- positive region of the spinal cord. After E18, the entire CNS is labeled, through adulthood. The mAb labels the surfaces of dissociated, living cells. Other, non-CNS areas of FORSE-1 labeling are nasal and otic placodes, nasal epithelium, nasal glands, and early (E9.5–10.5) endoderm. mAb FORSE-1 recognizes an epitope present on both a high- molecular-weight (> 200 kDa) proteoglycan from embryonic and early postnatal brain, and on a 80 kDa doublet that is restricted to the CNS in the adult. These findings suggest the FORSE-1 antigen as a candidate cell surface molecule for mediating regional specification from the earliest stages of CNS development.

Additional Information

© 1995 by Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN's website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). Received May 3. 1994; revised July 18, 1994; accepted July 25, 1994. We thank Dr. Didier Stainier for the 52G9 mAb, and Andrew Furley for helpful discussions leading to this experimental approach. We also thank Drs. Karen Allendoerfer, Lisa Banner, and Sue McConnell for offering useful comments on the manuscript, and Bob Turing, Richard Gomez, Ben Sewell, Lance Brown, Ella McClanahan, Jim Staub, Theo Steiner, Alice Edel, and Le Hanh Dinh from the Graphic Arts facility at Caltech for their assistance with the illustrations. This project was supported by grants from the Lucille P. Markey Charitable Trust, the NINOS, and the Amyotrophic Lateral Sclerosis Association to P.H.P., an NRSA from the NINDS to Z.K., and a Helen G. and Arthur Mccallum fellowship to S.T.

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August 20, 2023
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