Multiple lineage-specific roles of Smad4 during neural crest development
Multiple lineage-specific roles of Smad4 during neural crest development
复制标题
DOI：
10.1016/j.ydbio.2009.04.001
复制
发表时间：
2009-06-15
影响因子：
2.7
通讯作者：
Sommer, Lukas
中科院分区：
文献类型：
--
作者：
Buechmann-Moller, Stine;Miescher, Iris;Sommer, Lukas
在脊椎动物发育过程中，神经嵴细胞暴露于多种细胞外信号，这些信号驱动它们分化成神经和非神经细胞谱系。深入了解潜在参与神经嵴细胞在体内的命运决定的信号已经获得了细胞培养实验，允许识别有益的生长因子，促进多能神经嵴细胞的增殖或收购特定的命运。例如，TGF因子家族的成员诱导神经发生和平滑肌细胞形成，而代价是培养物中的其他命运。在体内，各种TGF信号传导成分的条件性消融导致神经嵴的非神经衍生物畸形，但尚不清楚这些表型是否涉及异常的命运决定。此外，神经元的决定是否确实需要体内TGF因子的活性仍有待证明。为了解决这些问题，我们有条件地删除了神经嵴中的Smad4，从而使所有典型的TGF β因子信号转导失活。令人惊讶的是，除了三叉神经节的感觉神经发生之外，这些突变体中的神经嵴细胞命运并未受到影响。相反，Smad4调节平滑肌的存活以及自主神经和ENS神经元祖细胞的增殖。因此，Smad信号在体内发挥多种谱系特异性作用，其中许多仅在神经嵴细胞命运决定后才被引发。(C)2009 Elsevier Inc. All rights reserved.
During vertebrate development, neural crest cells are exposed to multiple extracellular cues that drive their differentiation into neural and non-neural cell lineages. Insights into the signals potentially involved in neural crest cell fate decisions in vivo have been gained by cell culture experiments that have allowed the identification of instructive growth factors promoting either proliferation of multipotent neural crest cells or acquisition of specific fates. For instance, members of the TGF factor family induce neurogenesis and smooth muscle cell formation at the expense of other fates in culture. In vivo, conditional ablation of various TGF signaling components resulted in malformations of non-neural derivatives of the neural crest, but it is unclear whether these phenotypes involved aberrant fate decisions. Moreover, it remains to be shown whether neuronal determination indeed requires TGF factor activity in vivo. To address these issues, we conditionally deleted Smad4 in the neural crest, thus inactivating all canonical TGF beta factor signaling. Surprisingly, neural crest cell fates were not affected in these mutants, with the exception of sensory neurogenesis in trigeminal ganglia. Rather, Smad4 regulates survival of smooth muscle and proliferation of autonomic and ENS neuronal progenitor cells. Thus, Smad signaling plays multiple, lineage-specific roles in vivo, many of which are elicited only after neural crest cell fate decision. (C) 2009 Elsevier Inc. All rights reserved.