BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system

Autor: Nandor Nagy, Katherine C. Brewer, Adele M. Doyle, Drucilla J. Roberts, Allan M. Goldstein
Rok vydání: 2005
Předmět:
medicine.medical_specialty
Embryology
animal structures
Cellular differentiation
Genetic Vectors
Green Fluorescent Proteins
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein 4
Chick Embryo
Protein Serine-Threonine Kinases
Biology
Bone Morphogenetic Protein Receptors
Type II
Ligands
Bone morphogenetic protein
Enteric Nervous System
Cell Movement
Transforming Growth Factor beta
Internal medicine
medicine
Animals
Phosphorylation
Noggin
In Situ Hybridization
Body Patterning
Neurons
Neural crest
Cell Differentiation
Immunohistochemistry
Cell biology
Gastrointestinal Tract
Endocrinology
Bone morphogenetic protein 4
Neural Crest
Bone Morphogenetic Proteins
embryonic structures
Ganglion formation
Ganglia
Enteric nervous system
Neural crest cell migration
Carrier Proteins
Protein Binding
Signal Transduction
Developmental Biology
Zdroj: Mechanisms of Development. 122(6):821-833
ISSN: 0925-4773
DOI: 10.1016/j.mod.2005.03.003
Popis: The enteric nervous system (ENS) is derived from neural crest cells that migrate along the gastrointestinal tract to form a network of neurons and glia that are essential for regulating intestinal motility. Despite the number of genes known to play essential roles in ENS development, the molecular etiology of congenital disorders affecting this process remains largely unknown. To determine the role of bone morphogenetic protein (BMP) signaling in ENS development, we first examined the expression of bmp2, bmp4, and bmprII during hindgut development and find these strongly expressed in the ENS. Moreover, functional BMP signaling, demonstrated by the expression of phosphorylated Smad1/5/8, is present in the enteric ganglia. Inhibition of BMP activity by noggin misexpression within the developing gut, both in ovo and in vitro, inhibits normal migration of enteric neural crest cells. BMP inhibition also leads to hypoganglionosis and failure of enteric ganglion formation, with crest cells unable to cluster into aggregates. Abnormalities of migration and ganglion formation are the hallmarks of two human intestinal disorders, Hirschsprung's disease and intestinal neuronal dysplasia. Our results support an essential role for BMP signaling in these aspects of ENS development and provide a basis for further investigation of these proteins in the etiology of neuro-intestinal disorders.
Databáze: OpenAIRE
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