The bicoid-related Pitx gene family in development
The bicoid-related Pitx gene family in development
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DOI：
10.1007/s003359900970
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发表时间：
1999-02-01
期刊：
影响因子：
2.5
通讯作者：
Camper, SA
中科院分区：
文献类型：
--
作者：
Gage, PJ;Suh, H;Camper, SA
同源异型盒基因在后脑和轴体发育中的重要作用已被证实。最近，已经清楚的是，同源异型盒基因的某些亚家族在更前部结构的发育中起着特别重要的作用。这些包括眼睛中的配对基因家族（Gehring，1996; Hanson和货车Heyningen，1995; Macdonald和Wilson，1996; Wehr和Gruss，1996），前脑和中脑中的正齿和无远端基因家族（Acampora等人，1996; Acampora等人，1995; Price等人，1991; Simeone等人，1994;威廉姆斯，1998）和脑下垂体中的Lhx基因家族（Sheng等，1997; Sheng等人，1996年）。本文综述了新发现的Pitx基因家族及其在发育中的作用。这个家族包括三个已在多种生物体中克隆的脊椎动物旁系同源物和一个苍蝇同源物。该基因家族的两个成员的突变导致人类疾病或影响前部结构的出生缺陷。这个基因家族的命名已经复杂化了，因为成员已经被多个实验室克隆和唯一命名（表1）。该家族的第一个成员，小鼠Ptx 1（垂体同源框1）被分离为参与垂体前叶促皮质细胞中阿黑皮素原基因转录的转录因子（Lamonerie et al.，1996年）。然而，由于小鼠和人类中的一些pentaxin基因先前已被指定为Ptx基因符号，因此这个新同源框基因家族的三个小鼠旁系同源物的基因符号为Pitx1，Pitx2和Pitx3（小鼠基因组数据库）。在这篇综述中，我们采用了MGD的官方命名法，并建议，为了清楚起见，这种命名法也适用于其他生物。三种脊椎动物旁系同源物，Pitx 1，Pitx 2和Pitx 3，都已从小鼠和人类中克隆出来（表1和其中的参考文献）。一些旁系同源物也已从鸡（Pitx 1和Pitx 2）、爪蟾和斑马鱼（Pitx 2）以及大鼠（Pitx 3）中克隆（表1和其中的参考文献）。在两篇报道中，在功能测定中克隆了小鼠Pitx 1：在使用Pit-1作为诱饵的双杂交筛选中（Szeto等人，1996年，如前所述。通过Rieger综合征基因的定位克隆鉴定人PITX 2（Semina等人，1996年）的报告。在其他报道中，克隆是使用简并PCR或低严格性杂交来检测各种胚胎和成体组织中表达的同源框序列的结果。从非洲爪蟾和斑马鱼克隆Pitx 1的困难表明，这种直向同源物在自然界中可能不如Pitx 2那样广泛分布（Kitamura等人，1997年）。然而，最近在染色体步移过程中对蝇Pitx基因的鉴定表明，该基因家族在脊椎动物和无脊椎动物分化之前出现（Vorbruggen等人，1997年）。已在小鼠和人类中绘制了每种脊椎动物的遗传图谱（表1）。
The important roles of homeobox genes in development of the hindbrain and axial body are well established. More recently, it has become clear that certain subfamilies of homeobox genes play particularly important roles in the development of more anterior structures. These have included the paired gene family in the eye (Gehring, 1996; Hanson and Van Heyningen, 1995; Macdonald and Wilson, 1996; Wehr and Gruss, 1996), the orthodenticle and distalless gene families in the fore-and midbrains (Acampora et al., 1996; Acampora et al., 1995; Price et al., 1991; Simeone et al., 1994; Williams, 1998), and the Lhx gene family in the pituitary gland (Sheng et al., 1997; Sheng et al., 1996). This review summarizes the newly identified Pitx gene family and its role in development. This family includes three vertebrate paralogues that have been cloned in multiple organisms, and a fly cognate. Mutations in two members of this gene family lead to human disease or birth defects affecting anterior structures. The nomenclature for this gene family has been complicated by the fact that members have been cloned and uniquely named by more than one laboratory (Table 1). The first member of this family, mouse Ptx1 (pituitary homeobox 1) was isolated as a transcription factor involved in pro-opiomelanocortin gene transcription in anterior pituitary corticotropes (Lamonerie et al., 1996). However, since some pentaxin genes in mouse and human had previously been assigned the Ptx gene symbol, the gene symbols for the three mouse paralogues for this new homeobox gene family are Pitx1, Pitx2, and Pitx3 (Mouse Genome Database). In this review, we have adopted the official nomenclature of the MGD and propose that, for clarity, this nomenclature be adopted for other organisms.Three vertebrate paralogues, Pitx1, Pitx2, and Pitx3, have all been cloned from mouse and human (Table 1 and references therein). Some paralogues have also been cloned from chicken (Pitx1 and Pitx2), xenopus and zebrafish (Pitx2), and rat (Pitx3)(Table 1 and references therein). In two reports, mouse Pitx1 was cloned in functional assays: in a two-hybrid screen using Pit-1 as bait (Szeto et al., 1996) and as noted above. Human PITX2 was identified by positional cloning of the Rieger Syndrome gene (Semina et al., 1996). In the other reports, cloning was the result of using degenerate PCR or low stringency hybridization to detect expressed homeobox sequences in a variety of embryonic and adult tissues. The difficulty in cloning Pitx1 from xenopus and zebrafish has suggested that this orthologue may not be as widely distributed in nature as Pitx2 (Kitamura et al., 1997). However, the recent identification of a fly Pitx gene during a chromosome walk demonstrates that this gene family arose prior to the divergence of vertebrates and invertebrates (Vorbruggen et al., 1997). Each vertebrate paralogue has been mapped genetically in mouse and human (Table 1).