Development of LBP110 expression by neural crest-derived enteric precursors: migration and differentiation potential...

Neural crest-derived cells acquire a 110-kD laminin-binding protein (LBP110) when they colonize the murine bowel. Laminin stimulates LBP110-expressing cells to develop as neurons. We have followed the development of LBP110 by neural crest-derived cells as they enter the gut of control and ls/ls mutant mice. The expression of neurofilament and choline acetyltransferase was used as markers of a neuronal phenotype. Tyrosine hydroxylase was used as a marker for the mash-1-dependent lineage of enteric precursors, while calcitonin gene-related peptide was used as a marker for the mash-1-independent lineage of crest-derived cells. A subset of cells expressing LBP110 was located along the vagi at E10 at cervical and thoracic levels. At E12, cells expressing LBP110 extended from the foregut to the midgut. The expression of neurofilament protein lagged behind that of LBP110 by about 0.5 day and then became coincident with LBP110 immunoreactivity. By E15, cells doubly labeled with antibodies to LBP110 and neurofilament protein were located along the entire extent of the bowel up to but not including the terminal colon. By E16, both the proximal and terminal colon contained cells expressing LBP110 and neurofilaments. The pattern of immunoreactivity could not be distinguished between ls/ls and control animals prior to E16. By E16, when the terminal colon of control animals contained many cells expressing LBP110 and neurofilaments, the terminal colon of ls/ls animals lacked cells expressing these proteins; nevertheless, structures outside of the terminal colon were heavily endowed with cells expressing LBP110 and neurofilaments. These ectopically located cells derived from both mash-1-dependent and -independent lineages of crest-derived precursors.