Neuronal developmental marker FORSE-1 identifies a putative progenitor of the pulmonary neuroendocrine cell lineage during lung development.
The FORSE-1 (forebrain-surface-embryonic) monoclonal antibody (MAb) recognizes a carbohydrate cell surface epitope related to the Lewis-X (LeX) and stage-specific embryonic antigens (SSEAs). In the developing CNS, the FORSE-1 epitope is believed to serve as a marker of progenitor cells. We studied the expression of the FORSE-1 epitope in pulmonary neuroendocrine cells (PNECs) and related neuroepithelial bodies (NEBs), cell types implicated in paracrine regulation of lung development. We used dual immunolabeling to identify PNECs/NEBs in tissue sections from developing rabbit fetal lungs and corresponding primary lung cell cultures. During the early stage (E16), the FORSE-1 MAb labeled primitive airway epithelium, whereas serotonin (5HT) immunoreactivity, a marker of PNEC/NEB differentiation, was negative. After E18, FORSE-1 labeling became restricted to PNECs and NEBs, identified by co-expression with 5HT, then decreased coincident with an increase in 5HT. Expression of the FORSE-1 epitope correlated inversely with 5HT expression in PNEC/NEB cells. FORSE-1 immunoreactivity correlated with cell proliferation assessed by BrdU labeling. Downregulation of the FORSE-1 epitope correlated with maturation of PNECs/NEBs. The presence of few FORSE-1/5HT-positive cells in postnatal lung suggests retention of progenitors. The FORSE-1 epitope was associated with a high molecular weight (286 kD) glycoprotein that decreased with increasing gestational age, as demonstrated by immunoblotting. Overall expression of SSEA-1, -3, and -4 antigens was similar to FORSE-1/5HT, although the former was preferentially localized to neurite-like processes. Because the role of the FORSE-1 epitope in the CNS probably involves cell adhesion and differentiation, we propose a similar function in developing lung. The demonstration of LeX/SSEA antigen expression in the PNEC/NEB cell lineage underscores the importance of these cells in developing lung. Furthermore, the FORSE-1 antigen may identify committed progenitors of the PNEC/NEB cell system.
Pan
Jie
J
Department of Paediatric Laboratory Medicine, Hospital for Sick Children and University of Toronto, Ontario, Canada.
Yeger
Herman
H
Cutz
Ernest
E
D000818:Animals; D000954:Antigens, Surface; D002352:Carrier Proteins / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D006023:Glycoproteins / Q000378:metabolism; D007150:Immunohistochemistry; D016256:Lewis X Antigen / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018613:Microscopy, Confocal; D008970:Molecular Weight; D009474:Neurons / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism
D000954:Antigens, Surface; D002352:Carrier Proteins; D006023:Glycoproteins; D016256:Lewis X Antigen; D011509:Proteoglycans; C092260:antigen FORSE-1; D012701:Serotonin