Hox在发展基因:Hox代码

引用:迈尔斯,P。 (2008)Hox基因开发:Hox代码。自然教育 1 (1):2,http://scienceblogs.com/pharyngula/2007/09/the_hox_code.php

Hox基因,转录因子家族,是动物的主要监管机构的发展。然而,与大多数基因的顺序Hox基因在基因组所包含的意义。

Aa Aa Aa

的Hox基因是一组转录因子基因表现出一种不同寻常的属性:他们提供的一种方式基因表达被翻译成许多不同形式的动物(后生动物)展览。在大多数情况下,基因组似乎是一个大量的各种基因对随机分散,没有出现在他们安排在一个延续的订单才会显现在他们表达的过程发展。的Hox基因,相比之下,似乎理解结构的一个岛屿。这些基因指定段的身份甘心的胚胎将形成的一部分头、胸或腹部,也都是聚集在一起的一个(通常)整洁的地方。在这个集群,甚至有秩序的进一步证据。

Hox基因在Drosphila

为了更好地理解的安排和作用Hox基因,看一看果蝇图1的一部分。如图所示,在果蝇有八个Hox连续的基因,基因的顺序在这一行的言论反映了他们的订单飞的身体。左边的基因发现3 '末端的DNA链,表示实验室(唇),表达的头部;另一方面,该基因在DNA链的右端,Abd-B(Abdominal-B),表示结束的时候飞的腹部。

敲出个人Hox基因在果蝇导致同源转化变化——换句话说,一个身体部分发展到另一个。一个著名的例子就是Antennapedia突变体,腿发展动态的头而不是天线。的Hox级联的基因早期演员互动,使分段的动物形态不同的地区的发展。事实上,激活的Hox基因3 '末端的最早的诱因之一,领导发展划分为头的一部分。

Hox gene cluster.", "true", "Figure 1", "A schematic of the Hox gene clusters (not to scale) in the genomes of D. melanogaster and M. musculus. Genes are colored to differentiate between Hox family members, and genes that are orthologous between clusters and species are labeled in the same color. Genes are shown in the order in which they are found on the chromosomes but, for clarity, some non-Hox genes that are located within the clusters in the fly genome have been excluded. The positions of three non-Hox homeodomain genes, zen, bcd and ftz, are shown in the fly Hox cluster (grey boxes). Gene abbreviations: lab, labial; pb, proboscipedia; zen, zerknullt; bcd, bicoid; Dfd, Deformed; Scr, Sex combs reduced; ftz, fushi tarazu; Antp, Antennapedia; Ubx, Ultrabithorax; abd-A, abdominal-A; Abd-B, Abdominal-B.", "true", "All rights reserved.", '1126', '251', '//www.scienovate.com');"> 示意图显示包含Hox基因的基因簇的结构。d .腹基因组只包含一个Hox基因簇,而m .骶基因组包含四个Hox基因簇。基因在每个集群显示高集群和物种之间的同源性,这是由颜色编码,沿着集群放置规定的身体区域基因表达。

示意图显示包含Hox基因的基因簇的结构。d .腹基因组只包含一个Hox基因簇,而m .骶基因组包含四个Hox基因簇。基因在每个集群显示高集群和物种之间的同源性,这是由颜色编码,沿着集群放置规定的身体区域基因表达。

图1:基因组的组织Hox基因簇。

Hox gene cluster.", "true", "Figure 1", "A schematic of the Hox gene clusters (not to scale) in the genomes of D. melanogaster and M. musculus. Genes are colored to differentiate between Hox family members, and genes that are orthologous between clusters and species are labeled in the same color. Genes are shown in the order in which they are found on the chromosomes but, for clarity, some non-Hox genes that are located within the clusters in the fly genome have been excluded. The positions of three non-Hox homeodomain genes, zen, bcd and ftz, are shown in the fly Hox cluster (grey boxes). Gene abbreviations: lab, labial; pb, proboscipedia; zen, zerknullt; bcd, bicoid; Dfd, Deformed; Scr, Sex combs reduced; ftz, fushi tarazu; Antp, Antennapedia; Ubx, Ultrabithorax; abd-A, abdominal-A; Abd-B, Abdominal-B.", "true", "All rights reserved.", '1126', '251', '//www.scienovate.com');">的示意图Hox基因簇(规模)的基因组d .腹和m .所支配。基因是颜色的区分Hox家庭成员和集群和物种之间的同源的基因标记相同的颜色。基因所示顺序是染色体上发现的,但是为了清楚起见,一些非Hox基因位于集群在飞基因组中被排除在外。三个非的位置Hoxhomeodomain基因,禅,bcd和保税区,所示Hox集群(灰色框)。基因缩写:实验室唇;pbproboscipedia;禅zerknullt;bcdbicoid;目前企业畸形的;可控硅、性梳减少;保税区副食tarazu;AntpAntennapedia;UbxUltrabithorax;abd-Aabdominal-A;Abd-B,Abdominal-B。

Hox gene cluster.", "Figure 1", "A schematic of the Hox gene clusters (not to scale) in the genomes of D. melanogaster and M. musculus. Genes are colored to differentiate between Hox family members, and genes that are orthologous between clusters and species are labeled in the same color. Genes are shown in the order in which they are found on the chromosomes but, for clarity, some non-Hox genes that are located within the clusters in the fly genome have been excluded. The positions of three non-Hox homeodomain genes, zen, bcd and ftz, are shown in the fly Hox cluster (grey boxes). Gene abbreviations: lab, labial; pb, proboscipedia; zen, zerknullt; bcd, bicoid; Dfd, Deformed; Scr, Sex combs reduced; ftz, fushi tarazu; Antp, Antennapedia; Ubx, Ultrabithorax; abd-A, abdominal-A; Abd-B, Abdominal-B.", '1126','//www.scienovate.com', "The D. melanogaster Hox gene cluster contains eight genes, each with a specific gene name. From the 3' to 5' end of the chromosome (left to right), the eight genes are in the following order: lab, pb, Dfd, Scr, Antp, Ubx, abd-A, and Abd-B. The Hox gene names for M. musculus contain three parts: the word Hox; the letter a, b, c, or d based on the gene cluster in which the gene resides; and a number 1 through 13 based on the location of the gene along the gene cluster. Smaller numbers are located toward the left, or the 3' end of the chromosome, whereas larger numbers are located toward the right, or the 5' end of the chromosome. In addition, gene paralogs are given the same number in all mouse Hox gene clusters, and homologous genes display the same color in the diagram. Each of the mouse gene clusters contains only a subset of Hox genes, resulting in 2 to 4 paralogs for each gene. Hox1 genes are identified as the labial class, Hox4 through Hox8 are identified as the central class, and Hox9 through Hox13 are identified as the abdominal-B class.")" class="inlineLinks">细节图

Hox在老鼠和其他脊椎动物的基因

左边的图显示了正常的中轴骨鼠标,包括脊椎骨、肋骨、胸骨和尾巴。右边的骨架制剂的照片显示正常椎元素而改变椎元素与Hox5 paralogous删除有关,Hox6, Hox9 Hox10, Hox11。

图2:具体椎元素的变化Hox5、Hox6 Hox9 Hox10,和Hox11paralogous突变体。

在左边的面板中,显示了轴向骨架图,与特定的椎元素显示在右面板标志(C,颈;T,胸;L,腰椎,年代,骶)。野生型、控制元素从特定的脊椎位置都是用字母和数字。paralogous突变体的相似片段所示左和右,每个paralogous突变组的彩色盒子。

Hox5, Hox6, Hox9, Hox10, and Hox11 paralogous mutants.", "Figure 2", "On the left side of the panel, a diagram of the axial skeleton is shown, with specific vertebral elements shown in the right panel marked (C, cervical; T, thoracic; L, lumbar, S, sacral). Wild-type, control elements from specific vertebral positions are denoted by letter and number. The analogous segment from the paralogous mutants are shown on the right and left, with colored boxes for each paralogous mutant group.", '433','http://www.wiley.com', "In a normal mouse, a dorsal neural arch is found on the C2 vertebrae (arrow), ribs develop only on the thoracic vertebrae, and fused sacral wings are found at S1 to S4. When paralogous deletions of Hox genes are made, these features do not develop normally, resulting in skeletal deformities. For example, when the paralogous Hox5 genes are deleted, a dorsal neural arch appears on C7 and T1 (arrows) similar to the normal C2 vertebrae, and ribs are initiated but not completed on T1. When the paralogous Hox6 genes are deleted, no ribs form at T1. In contrast, when the Hox9 genes are deleted, additional ribs form at L1. Ribs are also formed from L1 to S1 when the Hox10 genes are deleted, and the fused sacral wings are absent at S1 in mice lacking Hox11.")" class="inlineLinks">细节图

现在检查鼠标图1的部分。脊椎动物,包括老鼠,Hox基因同源飞的,这些基因都聚集在离散位置3到5的顺序反映了前部,后部的表达式。有几个鼠标和飞之间的差异Hox然而,基因。一个明显的区别在于有更多Hox基因5 '端鼠标段;这些表达式对应的尾巴,和苍蝇没有任何同源的脊索动物的尾巴。另一个区别是,在鼠标,有四家银行Hox基因:HoxA、HoxB HoxC,和HoxD。脊椎动物有这些平行,重叠套Hox基因,这表明形态可能是一个产品的组合表达四个Hox基因的集群。这意味着可能存在Hox代码,在身份可以定义更多层次的范围通过混合的每一个基因的表达。

在飞,情况要简单得多。因为每一段或多或少表达只有一个Hox基因突变或击倒一个单身Hox基因会影响相应的身体部分。然而在脊椎动物,每段至少有两个,和在某些情况下四,Hox基因可能参与了它的发展。因此,有冗余的可能性。

例如,在老鼠,HoxA3基因表达在前颈椎,附近地区第一颈椎一端头骨。删除HoxA3没有检测到联合的影响;其影响力太微妙的衡量,它影响其他方面颈椎的规范,或伴侣基因,接管其工作。注意,在图1HoxA3有一个假字,或复制,叫什么HoxD3,这是表示在一个非常相似的地方。当HoxD3是变异本身有严重的异常;在这里,第一颈椎部分融合与头骨的基础。然而,敲门HoxA3和HoxD3显示,HoxA3毕竟是很重要的;没有它,第一颈椎不形式。事实上,在这种情况下,人们认为最初的中胚层组织骨彻底respecified与头骨相反,它完全融合成为头骨的基础的一部分。

这些结果告诉我们的结合Hox基因所需的适当发展第一颈椎。他们也复杂化分析表明淘汰了Hox基因一次鼠标不会导致的情况表型或部分表型将看到的,即使在基因领域具有重要的作用。最终,所有的paralogous基因需要淘汰出局。也就是说,为了看看第三Hox基因在集群中,例如,您需要执行一个paralogous删除破坏的功能HoxA3,HoxB3,HoxD3(没有HoxC3)来评估表型。

这种现象也在脊椎动物同源转化突变的原因之一很少见。在飞,一个基因突变,导致一个笼头变成了翅膀,或者天线变成一条腿;在鼠标,2 - 4基因必须同时删除类似的完整转换。

老鼠Paralogous淘汰赛

图3

Hox paralogous mutants.", "true", "Figure 3", "Different vertebral elements are denoted by unique shapes, shown in the bottom panel . Aqua-shaded areas demonstrate the regions of anterior homeotic transformations of the somite-derived primaxial phenotypes. Purple-shaded areas show the lateral plate-derived, abaxial phenotypes for each group. The orange background highlights the regions of phenotypic overlap between adjacent paralogous mutants.", "true", "All rights reserved.", '900', '623', 'http://www.wiley.com');"> Hox paralogous mutants.", "Figure 3", "Different vertebral elements are denoted by unique shapes, shown in the bottom panel . Aqua-shaded areas demonstrate the regions of anterior homeotic transformations of the somite-derived primaxial phenotypes. Purple-shaded areas show the lateral plate-derived, abaxial phenotypes for each group. The orange background highlights the regions of phenotypic overlap between adjacent paralogous mutants.", '900','http://www.wiley.com', "When Hox5 paralogs are deleted in a mouse, the ribs at T1 are initiated but not completely formed, and the T2 ribs are connected to the sternum at a position inferior to normal. When Hox6 is deleted, no ribs form at T1 and the ribs at T2 are incomplete. Deletion of Hox9 paralogs causes the inferior thoracic ribs to attach to the sternum, and ribs form on the L1 to L4 vertebrae. In addition, two extra lumbar vertebrae are formed. Hox10 deletion causes formation of T12-like ribs on the lumbar vertebrae and partial ribs on the sacral vertebrae as well. Hox11 deletion prevents the formation of fused sacral wings, and the sacral vertebrae and the superior tail vertebrae develop into lumbar vertebrae. Regardless of structural changes to individual vertebrae, the total number of vertebrae remains the same in all mice.")" class="inlineLinks">细节图

技术已经发展的研究人员开始发布描述的老鼠,有完整paralogous基因集淘汰出局。截面的脊椎从这些小鼠右侧的图2所示。中间列显示正常的控制,或椎骨应该是什么样子在nonmutant鼠标。两边是每个paralogous突变体的突变形式。

图片左边的图2说明了骨骼形态学评估。顶部是颈椎,通过C7 C1,这并不与肋骨。接下来是肋胸椎,通过T13 T1。T1通过T7也环绕连接到胸骨,这是远轴的骨架的一部分(椎骨primaxial骨架的一部分)。然后来了腰椎,L1通过社会、骶椎骨S1到S4与骨盆(表达),和许多小尾椎骨。这些骨头有一个离散的、可辨认的形态。

看看T1的控制。除了脊椎的椭圆形轮廓,应该有一双结实的肋骨。左边,与绿色,是一个完整的效果基因敲除——所有的Hox5基因HoxA5,HoxB5,HoxC5。在这里,肋骨开始形成,但他们是不完整的。这是一个局部变换对颈椎形态。向右,与紫色,是T1当所有的Hox6基因(HoxA6,HoxB6,HoxC6)取出;正如你所看到的,它看起来几乎一模一样的控制C7椎。这是一个完整的同源转化T1到C7的变换。

图4

Hox paralogous mutants.", "true", "Figure 4", "The regions for both primaxial and abaxial defects are shown as color-coded bars adjacent to the segments affected in paralogous mutants. Note the differences in AP position as well as the overlap differences in the primaxial versus the abaxial phenotypes.", "true", "All rights reserved.", '433', '400', 'http://www.wiley.com');"> Hox paralogous mutants.", "Figure 4", "The regions for both primaxial and abaxial defects are shown as color-coded bars adjacent to the segments affected in paralogous mutants. Note the differences in AP position as well as the overlap differences in the primaxial versus the abaxial phenotypes.", '433','http://www.wiley.com', "Deletion of Hox4, which is represented by an orange bar, affects C1 to C5 in the primaxial skeleton. Deletion of Hox5, which is represented by a red bar, affects C3 to T2 in the primaxial skeleton and T1 to T8 as well as the manubrium and xiphoid processes in the abaxial skeleton. Deletion of Hox6, represented by a green bar, affects C6 to T6 in the primaxial skeleton and T1 to T8 and the xiphoid process in the abaxial skeleton. Deletion of Hox9, represented by an aqua bar, affects T8 to L4 in the primaxial skeleton and T1 to T8 and the xiphoid process in the abaxial skeleton. Deletion of Hox10, which is represented by a blue bar, affects L1 to S4. Deletion of Hox11, which is represented by a purple bar, affects S1 through the first 5 segments of the caudal tail.")" class="inlineLinks">细节图

背视图说明这些paralogous淘汰赛的影响如图3所示。每个基因敲除影响特定的地区。当所有的Hox9基因突变,例如,我们看到一个前midtrunk转变。后胸段现在肋骨,满足sternum-as如果T8通过T13正试图通过T7 T1。此外,一些胸腰椎获得字符,发芽的肋骨,那里应该没有。与这些更完整的淘汰赛的假字、同源转化转换到处都可以看到!

每一个Hox假字控制一个特定的形态域。注意,不仅有组合安排在一个假字银行(这些微妙之处并不如图4所示),但也有套假字的组合。骶段,例如,定义的表达式Hox10和Hox11个基因可以想象一种逻辑门在监管电路开关下游基因信号所需的特定形态加入骨盆只在两组Hox基因的存在。其他实验表明,基态的一段要thoracic-like和开发的四肢;Hox10和Hox11也可能功能抑制肋骨形成。

了解身体模式通过Hox基因

什么Hox代码所代表的是一个有些数字调节轴向模式的机制。混合和匹配组合的一小部分的表达Hox生物基因,产生更大范围的形态的可能性。Wellick中所描述的实验总结(Wellick, 2007),而粗糙的水平,揭示广泛的块Hox监管计划,但未来的工作应该提炼出细节,包括特定的形态和细节方面的监管。基因控制的身体形状是comprehend-but艰难的过程Hox系统是一个地方的研究人员正在接近理解这个过程。