RARγ and Cdx1 interactions in vertebral patterning
RARγ and Cdx1 interactions in vertebral patterning
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DOI：
10.1006/dbio.2001.0455
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发表时间：
2001-12-01
影响因子：
2.7
通讯作者：
Lohnes, D
中科院分区：
文献类型：
--
作者：
Allan, D;Houle, M;Lohnes, D
外源维甲酸(RA)在原肠后期给药时可引起椎体顺位。这些椎体的改变与前椎骨中HOX基因表达的吻端极限的改变有关，表明维甲酸信号调节了决定椎体特性的HOX基因的组合表达。相反，某些RA受体(RAR)的缺失会导致主要影响宫颈区域的前部同源异型转化。尽管有这些观察，但维甲酸信号、体细胞HOX表达和椎体模式之间的关系还知之甚少。小鼠CDX家族的成员(CDX1、CDX2和CDX4)是果蝇尾部的同源基因，编码含有同源框的转录因子。CDX1纯合子缺失突变体表现出前同源异型转化，其中一些突变使人想起RAR伽马缺失后代的转化。在CDX1突变体中，这些转化伴随着某些HOX基因在椎前的后部化表达。CDX1最近被证明是一个直接的RA靶点，这表明维甲酸信号可能通过一种间接的方式影响脊椎模式。为了进一步研究这种关系，我们产生了一系列完整的CDX1-RAR伽马突变体，并对正常妊娠或服用RA后的骨骼表型进行了评估。在复合突变体中观察到这些无效等位基因之间的协同作用，外源RA对脊椎形态发生的完全影响需要CDX1。这些发现与RA在CDX1上游关于轴向模式的作用是一致的。然而，外源RA减弱了CDX1缺失突变体固有的几个缺陷。这一发现，再加上RAR Gamma-CDx1双零突变体相对于单空突变体表型严重性的增加，表明这些途径也是平行发挥作用的，可能是通过聚集在共同的靶上。(C)2001年学术出版社。
Exogenous retinoic acid (RA) can evoke vertebral homeosis when administered during late gastrulation. These vertebral transformations correlate with alterations of the rostral limit of Hox gene expression in the prevertebrae, suggesting that retinoid signaling regulates the combinatorial expression of Hox genes dictating vertebral identity. Conversely, loss of certain RA receptors (RARs) results in anterior homeotic transformations principally affecting the cervical region. Despite these observations, the relationship between retinoid signaling, somitic Hox expression, and vertebral patterning is poorly understood. The members of the murine Cdx family (Cdx1, Cdx2, and Cdx4) are the homologues of Drosophila caudal and encode homeobox-containing transcription factors. Cdx1 homozygous null mutants exhibit anterior homeotic transformations, some of which are reminiscent of those in RAR gamma null offspring. in Cdx1 mutants, these transformations occur concomitant with posteriorized prevertebral expression of certain Hox genes. Cdx1 has recently been demonstrated to be a direct RA target, suggesting an indirect means by which retinoid signaling may impact vertebral patterning. To further investigate this relationship, a complete allelic series of Cdx1-RAR gamma mutants was generated and the skeletal phenotype assessed either following normal gestation or after administration of RA. Synergistic interactions between these null alleles were observed in compound mutants, and the full effects of exogenous RA on vertebral morphogenesis required Cdx1. These findings are consistent with a role for RA upstream of Cdx1 as regards axial patterning. However, exogenous RA attenuated several defects inherent to Cdx1 null mutants. This finding, together with the increased phenotypic severity of RAR gamma -Cdx1 double null mutants relative to single nulls, suggests that these pathways also function in parallel, likely by converging on common targets. (C) 2001 Academic Press.