THE ALPHA-1 SUBUNIT OF LAMININ-1 PROMOTES THE DEVELOPMENT OF NEURONS BY INTERACTING WITH LBP110 EXPRESSED BY NEURAL CREST-DERIVED CELLS IMMUNOSELECTED FROM THE FETAL MOUSE GUT

A plasmalemmal protein, LDP110, which hinds to the alpha 1 chain of la minin-1, is acquired by the neural crest-derived precursors of enteric neurons after they colonize the gut, We tested the hypothesis that la minin-1 interacts with LBP110 to promote enteric neuronal development, The effects of laminin-1 on neuronal development were studied in cult ures of cells immunoselected from fetal mouse gut (E14-15) with antibo dies to LBP110 or p7S(NTR), a marker for enteric crest-derived cells, No matter which antibody was used, the development of cells expressing neuronal markers was increased three- to fourfold by culturing the ce lls on a laminin-1-containing substrate, To determine whether this eff ect of laminin-1 is due to the selective adherence of a neurocompetent subset of precursors, immunoselected cells were permitted to preadher e to poly-D-lysine. Addition of soluble laminin-1 24 h later promoted neuronal but glial development. The laminin-1-induced increment in neu ronal development was abolished both by a peptide containing the seque nce a the LRP110-binding domain, IKVAV, and by antibodies to laminin a lpha 1 that recognize the IKVAV domain, Neither reagent affected the t otal number of cells, In contrast, the response to laminin-1 was not a ffected by control peptides, preimmune sera, or antibodies to laminin beta 1. Laminin-1 transiently induced the expression of nuclear Fos im munoreactivity; this action mas blocked specifically by the IKVAV pept ide. These data are consistent with the hypothesis that LBP110 interac ts with the IKVAV domain of laminin alpha 1 to promote the differentia tion of neurons from enteric crest-derived precursors. (C) 1997 John W iley & Sons, Inc.