Basement membrane exposure defines a critical window of competence for pancreatic duct differentiation from undifferentiated pancreatic precursor cells

We previously showed that the undifferentiated pancreatic epithelium can di fferentiate into islets, ducts, or acini depending on its milieu and that l aminin is necessary for pancreatic duct formation. Therefore we wanted to s tudy the plasticity of laminin-induced duct differentiation the better to u nderstand mechanisms of pancreatic duct lineage selection induced by baseme nt membrane. Mouse embryonic pancreases were dissected at gestational day 1 1 (E11.5), and epithelium was isolated from its surrounding mesenchyme. Som e epithelia were cultured in a collagen gel devoid of laminin. These epithe lia were "rescued" at days 1-7 of culture by transferring them to a laminin -rich matrix (Matrigel) for 7 additional days. Other epithelia were instead first cultured in Matrigel, and then placed into collagen. Immunohistochem istry was performed for insulin, amylase, and carbonic anhydrase II. Pancre atic epithelia rescued from collagen into laminin during days lit after har vest were still able to form ducts, whereas epithelia deprived of laminin f or longer than this 4-day window were not. Pancreatic epithelia exposed to laminin for as little as 1 day, and then placed into collagen, still retain ed the ability to make ducts. Thus there is a clear cut-off in the developm ent of the pancreatic epithelium at E11.5, after which laminin appears nece ssary to induce duct formation. We believe that such "windows of competence " in embryonic development imply that developmental programs in the embryo allow some flexibility.