Ectopic expression of Gcm1 induces congenital spinal cord abnormalities.
Brief ectopic expression of Gcm1 in mouse embryonic tail bud profoundly affects the development of the nervous system. All mice from 5 independently derived transgenic lines exhibited either one or both of two types of congenital spinal cord pathologies: failure of the neural tube to close (spina bifida) and multiple neural tubes (diastematomyelia). Because the transgene is expressed only in a restricted caudal region and only for a brief interval (E8.5 to E13.5), there was no evidence of embryonic lethality. The dysraphisms develop during the period and within the zone of transgene expression. We present evidence that these dysraphisms result from an inhibition of neuropore closure and a stimulation of secondary neurulation. After transgene expression ceases, the spinal dysraphisms are progressively resolved and the neonatal animals, while showing signs of scarring and tissue resorption, have a closed vertebral column. The multiple spinal cords remain but are enclosed in a single spinal column as in the human diastematomyelia. The animals live a normal life time, are fertile and do not exhibit any obvious weakness or motor disabilities.
Department of Molecular, Cellular and Developmental Biology and. Department of Radiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Brahim
B
Nait-Oumesmar
Barbara
B
Stecca
Girish
G
Fatterpekar
Thomas
T
Naidich
Joshua
J
Corbin
Robert A
RA
Lazzarini
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins; D009436:Neural Tube Defects / Q000196:embryology / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics* / Q000502:physiology*; D009687:Nuclear Proteins; D013116:Spinal Cord / Q000002:abnormalities* / Q000196:embryology*; D016135:Spinal Dysraphism / Q000196:embryology / Q000235:genetics; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C491089:GCM1 protein, human; C101631:Gcm1 protein, mouse; C115962:HOXA7 protein, human; D018398:Homeodomain Proteins; C492047:Hoxa7 protein, mouse; D009363:Neoplasm Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D014157:Transcription Factors