Lmx1b-Expressing Cells in the Mouse Limb Bud Define a Dorsal Mesenchymal Lineage Compartment
Lmx1b-Expressing Cells in the Mouse Limb Bud Define a Dorsal Mesenchymal Lineage Compartment
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DOI：
10.1002/dvg.20430
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发表时间：
2009-04-01
期刊：
影响因子：
1.5
通讯作者：
Johnson, Randy L.
中科院分区：
文献类型：
--
作者：
Qiu, Qiong;Chen, Haixu;Johnson, Randy L.
lim同源结构域转录因子lmx1b是脊椎动物背-腹侧肢体模式的关键调节因子。在小鼠胚胎中，lmx1b最初在早期阶段的大多数（如果不是全部）肢芽细胞中转录，但随后迅速局限于背侧间充质细胞，在背侧阳性和腹侧阴性表达域之间有明显的界限。这种表达模式最初是如何建立的尚不清楚，表达lmx1b细胞和不表达lmx1b细胞之间维持明显背腹边界的机制也不清楚。在这里，我们采用遗传命运定位方法来确定从lmx1b的广泛表达域到受限制的背侧表达域的转变涉及到假定的腹侧细胞中lmx1b表达的选择性丧失。此外，我们发现一旦lmx1b的表达仅限于背侧间质细胞，这些细胞就会形成一个基于谱系的隔室，阻止背侧和腹侧细胞之间的混合，这与最近在鸡和小鼠中进行的命运定位实验一致（Pearse et al., 2007, Dev Biol 310:388-400; Arques et al., 2007, Development 134:3713-3722）。此外，lmx1b活性是维持而不是建立背间质室所必需的，这可能是通过一种涉及差异细胞粘附的机制实现的。综上所述，我们的研究结果表明，表达lmx1b的细胞定义了一个背肢芽间质谱系区，而这个区的维持取决于lmx1b的功能。创世纪47:24 - 233,2009。(C) 2009 Wiley-Liss, Inc。
The LIM-homeodomain transcription factor lmx1b is a critical regulator of vertebrate dorsal-ventral limb patterning. In the mouse embryo, lmx1b is initially transcribed throughout most, if not all, limb bud cells at early stages, but then rapidly becomes restricted specifically to dorsal mesenchymal cells with a sharp boundary between the dorsal-positive and ventral-negative expression domains. How this expression pattern is initially established is not well understood, nor are mechanism(s) that maintain a sharp dorsal-ventral boundary between lmx1b expressing and nonexpressing cells. Here, we employ a genetic fate mapping approach to establish that the transition from a broad expression domain of lmx1b to a restricted dorsal domain of expression involves selective loss of lmx1b expression in presumptive ventral cells. In addition, we show that once lmx1b expression becomes restricted to dorsal mesenchyme cells, these cells form a lineage-based compartment that prevents mixing between dorsal and ventral cells, consistent with recent fate mapping experiments carried out the chick and mouse (Pearse et al., 2007, Dev Biol 310:388-400; Arques et al., 2007, Development 134:3713-3722). Moreover, lmx1b activity is required to maintain, but not to establish the dorsal mesenchymal compartment likely through a mechanism involving differential cell adhesion. Taken together, our results indicate that lmx1b expressing cell define a dorsal limb bud mesenchymal lineage compartment and that maintenance of this compartment depends on lmx1b function. genesis 47:224-233, 2009. (C) 2009 Wiley-Liss, Inc.