ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right patterning in the mouse
ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right patterning in the mouse
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DOI：
10.1128/mcb.24.21.9383-9389.2004
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发表时间：
2004-11-01
影响因子：
5.3
通讯作者：
Ibáñez, CF
中科院分区：
文献类型：
--
作者：
Jörnvall, H;Reissmann, E;Ibáñez, CF
脊椎动物发育过程中的中内胚层形成和左右模式依赖于转化生长因子P超家族的选定成员，特别是Nodal和Nodal相关配体。已经鉴定了Nodal的两种I型丝氨酸/苏氨酸激酶受体ALK 4和ALK 7。缺乏ALK 4的小鼠胚胎不能产生中内胚层，并在原肠胚形成后不久死亡，类似于Nodal敲除小鼠的表型。ALK 4是否有助于左右模式仍然是未知的。在这里，我们报告了缺乏ALK 7的小鼠的产生和初步表征。纯合子突变小鼠以预期的频率出生，并保持活力和生育能力。在ALK 7（-/-）; Nodal（+/-）和ALK 7（-/-）; ALK 4（+/-）复合突变体中，断奶时的活力与野生型没有差异。ALK 7和ALK 4在发育中的肢芽的趾间区域高度表达。然而，ALK 7突变小鼠没有显示骨骼异常或肢体畸形。在携带Nodal或编码ActRIIA和ActRIIB共受体的基因突变的小鼠中鉴定的左右模式异常和器官发生缺陷，包括心脏畸形、肺异构、右侧肠道和脾发育不全，在缺乏ALK 7的小鼠中未观察到。最后，小脑、皮质和海马的组织学组织（啮齿动物脑中ALK 7显著表达的所有部位）在ALK 7突变小鼠中表现正常。我们得出结论，ALK 7不是小鼠中内胚层形成和左右图案化过程中Nodal信号传导的重要介质，但可能在特定组织和器官的发育或功能中介导Nodal和相关配体的其他活动。
Mesendoderm formation and left-right patterning during vertebrate development depend upon selected members of the transforming growth factor P superfamily, particularly Nodal and Nodal-related ligands. Two type I serine/threonine kinase receptors have been identified for Nodal, ALK4 and ALK7. Mouse embryos lacking ALK4 fail to produce mesendoderm and die shortly after gastrulation, resembling the phenotype of Nodal knockout mice. Whether ALK4 contributes to left-right patterning is still unknown. Here we report the generation and initial characterization of mice lacking ALK7. Homozygous mutant mice were born at the expected frequency and remained viable and fertile. Viability at weaning was not different from that of the wild type in ALK7(-/-); Nodal(+/-) and ALK7(-/-); ALK4(+/-) compound mutants. ALK7 and ALK4 were highly expressed in interdigital regions of the developing limb bud. However, ALK7 mutant mice displayed no skeletal abnormalities or limb malformations. None of the left-right patterning abnormalities and organogenesis defects identified in mice carrying mutations in Nodal or in genes encoding ActRIIA and ActRIIB coreceptors, including heart malformations, pulmonary isomerism, right-sided gut, and spleen hypoplasia, were observed in mice lacking ALK7. Finally, the histological organization of the cerebellum, cortex, and hippocampus, all sites of significant ALK7 expression in the rodent brain, appeared normal in ALK7 mutant mice. We conclude that ALK7 is not an essential mediator of Nodal signaling during mesendoderm formation and left-right patterning in the mouse but may instead mediate other activities of Nodal and related ligands in the development or function of particular tissues and organs.