Protein kinase A deficiency causes axially localized neural tube defects in mice.
We have studied the function of protein kinase A (PKA) during embryonic development using a PKA-deficient mouse that retains only one functional catalytic subunit allele, either Calpha or Cbeta, of PKA. The reduced PKA activity results in neural tube defects that are specifically localized posterior to the forelimb buds and lead to spina bifida. The affected neural tube has closed appropriately but exhibits an enlarged lumen and abnormal neuroepithelium. Decreased PKA activity causes dorsal expansion of Sonic hedgehog signal response in the thoracic to sacral regions correlating with the regions of morphological abnormalities. Other regions of the neural tube appear normal. The regional sensitivity to changes in PKA activity indicates that downstream signaling pathways differ along the anterior-posterior axis and suggests a functional role for PKA activation in neural tube development.
Huang
Yongzhao
Y
Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Roelink
Henk
H
McKnight
G Stanley
GS
D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015153:Blotting, Western; D001842:Bone and Bones / Q000378:metabolism; D020134:Catalytic Domain; D017868:Cyclic AMP-Dependent Protein Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000196:embryology; D009436:Neural Tube Defects / Q000235:genetics*; D015398:Signal Transduction; D013997:Time Factors
D017868:Cyclic AMP-Dependent Protein Kinases