Granata Alessandra, Quaderi Nandita A
MRC Centre for Developmental Neurobiology, King's College London, 4th Floor New Hunt's House, Guy's Hospital Campus, SE1 1UL, London, UK.
Dev Biol. 2003 Jun 15;258(2):397-405. doi: 10.1016/s0012-1606(03)00131-3.
Patterning the avian left-right (L/R) body axis involves the establishment of asymmetric molecular signals on the left and right sides of Hensen's node. We have examined the role of the chick Midline 1 gene, cMid1, in generating asymmetric gene expression in the node. cMid1 is initially expressed bilaterally, but its expression is then confined to the right side of the node. We show that this restriction of cMid1 expression is a result of repression by Shh on the left side of the node. Misexpression of cMid1 on the left side of the node results in bilateral Bmp4 expression and a loss of Shh expression. Correspondingly, downstream left pathway genes are repressed while right pathway genes are ectopically activated. Conversely, knocking down endogenous right-sided cMid1 results in a loss of Bmp4 expression and bilateral Shh expression. This results in an absence of right pathway genes and the ectopic activation of the left pathway on the right. Here, we present a revised model for the establishment of asymmetric gene expression in Hensen's node based on the epistatic interactions observed between Shh, cMid1, and Bmp4.
构建鸟类左右（L/R）体轴涉及在亨氏节左右两侧建立不对称的分子信号。我们研究了鸡的中线1基因（cMid1）在节点中产生不对称基因表达的作用。cMid1最初在两侧表达，但随后其表达局限于节点右侧。我们表明，cMid1表达的这种限制是由于节点左侧的Shh抑制作用。在节点左侧错误表达cMid1会导致双侧Bmp4表达以及Shh表达缺失。相应地，下游左侧通路基因被抑制，而右侧通路基因被异位激活。相反，敲低内源性右侧cMid1会导致Bmp4表达缺失以及双侧Shh表达。这导致右侧通路基因缺失以及左侧通路在右侧的异位激活。在此，我们基于观察到的Shh、cMid1和Bmp4之间的上位相互作用，提出了一个关于在亨氏节中建立不对称基因表达的修订模型。
