Intercellular signals downstream of endothelin receptor-B mediate colonization of the large intestine by enteric neuroblasts.
Mice homozygous for the piebald lethal (sl) mutation, which have a complete deletion of endothelin receptor-B, fail to form ganglion cells in the distal large intestine and are nearly devoid of cutaneous melanocytes. These phenotypic features stem from incomplete colonization of the hindgut and skin by neural crest-derived neuroblasts and melanoblasts, respectively. We have used expression of a transgene, dopamine-beta-hydroxylase-nlacZ, to study colonization of the enteric nervous system in sl/sl embryos and sl/sl <--> wild-type chimeric mice. Enteric neuroblasts derived from the vagal neural crest colonize the developing foregut, midgut and distal small intestine of sl/sl embryos in a cranial-to-caudal manner indistinguishable from sl/+ or +/+ embryos. However, colonization of the large intestine is retarded and the distal large intestine is never colonized, a developmental defect identical to that observed in lethal spotted (endothelin-3 deficient) embryos. The coat pigmentation and relative distributions of mutant and wild-type ganglion cells in sl/sl <--> wild-type chimeras indicate that the defect associated with endothelin receptor-B gene deletion is not strictly neuroblast autonomous (independent of environmental factors). Instead, intercellular interactions downstream of the endothelin receptor-B mediate complete colonization of the skin and gut by neural crest cells.
Kapur
R P
RP
Department of Pathology, Children's Hospital, Seattle, Washington, USA.
Sweetser
D A
DA
Doggett
B
B
Siebert
J R
JR
Palmiter
R D
RD
D000818:Animals; D017615:Enteric Nervous System / Q000196:embryology; D017353:Gene Deletion; D005838:Genotype; D008544:Melanocytes / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017466:Receptors, Endothelin