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.

Cloning of a Mouse β1,3N-Acetylglucosaminyltransferase GlcNAc(β1,3)Gal(β1,4)Glc-ceramide Synthase Gene Encoding the Key Regulator of Lacto-series Glycolipid Biosynthesis

“…7A, arrows). This discontinuous ventricular expression pattern is very similar to that reported previously with monoclonal antibodies 7A in the mouse (29) and FORSE-1 in the rat (30). Both antibodies recognize fucosylated neolacto-glycolipids bearing Lewis-X structures (3Ј-fucosyllactosamine), which are the predominant carriers of the Lewis-X determinant in the embryonic rodent cortex.…”

Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage

“…2H). These results are compatible with data in mouse development where Forse1 predominantly marks forebrain precursor cells (Tole et al 1995).…”

“…Cultures of early hESC-derived neural rosettes are not homogenous and can contain differentiated neurons, neural crest deriva-tives, nonneural derivatives, or undifferentiated hESCs. Forse1 was originally isolated as an antibody recognizing a surface epitope expressed in neuroepithelial cells derived upon RA-induction of the human embryonal carcinoma cell line NT2D1 (Tole et al 1995). A recent study reported Forse1 expression in a subset of hESCderived neural progeny (Pruszak et al 2007).…”

Human Cytomegalovirus Infection of Human Embryonic Stem Cell-Derived Primitive Neural Stem Cells Is Restricted at Several Steps but Leads to the Persistence of Viral DNA

“…FORSE-1 is an antibody that recognizes a specific, as-yet-undefined configuration of the Lewis X glycan (15). In rat embryos, FORSE-1 stains the anterior portion of the neural tube and developing brain, and its epitope appears to be primarily present on two neutral glycolipids (37).…”