Protein kinase A deficiency causes axially localized neural tube defects in mice

被引:83
作者
Huang, YZ
Roelink, H
McKnight, GS [1 ]
机构
[1] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA
关键词
D O I
10.1074/jbc.M111412200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:19889 / 19896
页数:8
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