The alpha1 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, LBP110, which binds to the alpha1 chain of laminin-1, is acquired by the neural crest-derived precursors of enteric neurons after they colonize the gut. We tested the hypothesis that laminin-1 interacts with LBP110 to promote enteric neuronal development. The effects of laminin-1 on neuronal development were studied in cultures of cells immunoselected from fetal mouse gut (E14-15) with antibodies to LBP110 or p75NTR, 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 cells on a laminin-1-containing substrate. To determine whether this effect of laminin-1 is due to the selective adherence of a neurocompetent subset of precursors, immunoselected cells were permitted to preadhere to poly-D-lysine. Addition of soluble laminin-1 24 h later promoted neuronal but not glial development. The laminin-1-induced increment in neuronal development was abolished both by a peptide containing the sequence of the LBP110-binding domain, IKVAV, and by antibodies to laminin alpha1 that recognize the IKVAV domain. Neither reagent affected the total number of cells. In contrast, the response to laminin-1 was not affected by control peptides, preimmune sera, or antibodies to laminin beta1. Laminin-1 transiently induced the expression of nuclear Fos immunoreactivity; this action was blocked specifically by the IKVAV peptide. These data are consistent with the hypothesis that LBP110 interacts with the IKVAV domain of laminin alpha1 to promote the differentiation of neurons from enteric crest-derived precursors.
Chalazonitis
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Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Tennyson
V M
VM
Kibbey
M C
MC
Rothman
T P
TP
Gershon
M D
MD
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017615:Enteric Nervous System / Q000166:cytology / Q000196:embryology; D005260:Female; D005333:Fetus / Q000166:cytology / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D018189:Immunomagnetic Separation; D007422:Intestines / Q000737:chemistry / Q000166:cytology / Q000294:innervation; D007797:Laminin / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology*; D016900:Neurofilament Proteins / Q000032:analysis / Q000276:immunology; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000276:immunology; D012995:Solubility; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology
D002352:Carrier Proteins; D007797:Laminin; C085259:Lamr2 protein, mouse; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C083321:isoleucyl-lysyl-valyl-alanyl-valine