Loss of the Prader-Willi syndrome protein necdin causes defective migration, axonal outgrowth, and survival of embryonic sympathetic neurons.
Prader-Willi syndrome is a neurodevelopmental disorder marked by abnormalities in feeding, drinking, thermoregulation, intestinal motility, and reproduction, suggesting disruption of the autonomic nervous system. Necdin, one of several proteins genetically inactivated in individuals with Prader-Willi syndrome, is important for the differentiation of central and sensory neurons. We now show that formation, migration, and survival of sympathetic superior cervical ganglion neurons are impaired in Ndn-null embryos. We observed reduced innervation of superior cervical ganglion target organs, including the submandibular gland, parotid gland, and nasal mucosa. While the formation of other sympathetic chain ganglia is unaffected, axonal extension is impaired throughout the sympathetic nervous system. These results demonstrate a novel role for necdin in cellular migration, in addition to its roles in survival and axon outgrowth. Furthermore, reduced sympathetic function provides a plausible explanation for deficiencies of salivary gland function in individuals with congenital necdin deficiency consequent to Prader-Willi syndrome.
Tennese
Alysa A
AA
Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
Gee
Christopher B
CB
Wevrick
Rachel
R
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011218:Prader-Willi Syndrome / Q000235:genetics / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000196:embryology / Q000378:metabolism / Q000473:pathology
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C069766:necdin