title: The location and phenotype of proliferating neural-crest-derived cells in the developing mouse gut.
abstract: Neural crest cells that originate in the caudal hindbrain migrate into and along the developing gastrointestinal tract to form the enteric nervous system. While they are migrating, neural-crest-derived cells are also proliferating. Previous studies have shown that the expression of glial-derived neurotrophic factor (GDNF) and endothelin-3 is highest in the embryonic caecum, and that GDNF alone or in combination with endothelin-3 promotes the proliferation of enteric neural-crest-derived cells in vitro. However, whether neural proliferative zones, like those in the central nervous system, are found along the developing gut is unknown. We used a fluorescent nucleic acid stain to identify dividing cells or BrdU labelling (2 h after administration of BrdU to the mother), combined with antibodies specific to neural crest cells to determine the percentage of proliferating crest-derived cells in various gut regions of embryonic day 11.5 (E11.5) and E12.5 mice. The rate of proliferation of crest-derived cells did not vary significantly in different regions of the gut (including the caecum) or at different distances from the migratory wavefront of vagal crest-derived cells. The phenotype of mitotic enteric crest-derived cells was also examined. Cells expressing the pan-neuronal markers, neurofilament-M and Hu, or the glial marker, S100b, were observed undergoing mitosis. However, no evidence was found for proliferation of cells expressing neuron-type-specific markers, such as nitric oxide synthase (at E12.5) or calcitonin gene-related peptide (at E18.5). Thus, for enteric neurons, exit from the cell cycle appears to occur after the expression of pan-neuronal proteins but prior to the expression of markers of terminally differentiated neurons.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, 3010, Melbourne, Victoria, Australia. h.young@unimelb.edu.au
authors.forename: H M
authors.initials: HM
authors.lastname: Young
authors.forename: K N
authors.initials: KN
authors.lastname: Turner
authors.forename: A J
authors.initials: AJ
authors.lastname: Bergner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D049109:Cell Proliferation; D019334:Endothelin-3 / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D010641:Phenotype
chemical_list: D015415:Biomarkers; D019334:Endothelin-3; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors