Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm
Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm
复制标题
DOI：
10.1101/gad.12.24.3910
复制
发表时间：
1998-12-15
影响因子：
10.5
通讯作者：
Michelson, AM
中科院分区：
文献类型：
--
作者：
Carmena, A;Gisselbrecht, S;Michelson, AM
中胚层祖细胞在果蝇胚胎中由表达l'sc的致死细胞的离散簇产生。使用遗传功能丧失和有针对性的异位表达方法，我们在这里证明，个别祖细胞指定的独特组合的细胞间信号的顺序部署。最初，无翼（Wg）和十肢麻痹（Dpp）表达结构域之间的交叉划分了外胚层预模式，该外胚层预模式以L 'sc预簇的形式印在相邻的中胚层上。该前群内的所有中胚层细胞都能够对由两种受体酪氨酸激酶（RTK）介导的后续指导性信号作出反应，所述受体酪氨酸激酶为果蝇表皮生长因子受体（DER）和无情（Htl）成纤维细胞生长因子受体。通过监测丝裂原相关蛋白激酶（MAPK）的二磷酸化形式的表达，我们发现这些RTK在原始感受态结构域内的小簇细胞中被激活。每个簇代表一个等价组，因为所有成员最初在L'sc和中胚层身份基因的表达方面类似于祖细胞。因此，局部RTK活动诱导中胚层等效组的形成。在神经原性基因的后续抑制影响下，RTK在从每个簇中出现的单个祖细胞中保持活性。此外，DER和Htl差异参与特定祖细胞的特化。我们得出结论，不同的细胞身份代码产生的WG，DPP，EGF和FGF信号的组合活动，在胚胎中胚层细胞的逐步确定。
Mesodermal progenitors arise in the Drosophila embryo from discrete clusters of lethal of scute (l'sc)-expressing cells. Using both genetic loss-of-function and targeted ectopic expression approaches, we demonstrate here that individual progenitors are specified by the sequential deployment of unique combinations of intercellular signals. Initially, the intersection between the Wingless (Wg) and Decapentaplegic (Dpp) expression domains demarcate an ectodermal prepattern that is imprinted on the adjacent mesoderm in the form of a L'sc precluster. All mesodermal cells within this precluster are competent to respond to a subsequent instructive signal mediated by two receptor tyrosine kinases (RTKs), the Drosophila epidermal growth factor receptor (DER) and the Heartless (Htl) fibroblast growth factor receptor. By monitoring the expression of the diphosphorylated form of mitogen-associated protein kinase (MAPK), we found that these RTKs are activated in small clusters of cells within the original competence domain. Each cluster represents an equivalence group because all members initially resemble progenitors in their expression of both L'sc and mesodermal identity genes. Thus, localized RTK activity induces the formation of mesodermal equivalence groups. The RTKs remain active in the single progenitor that emerges from each cluster under the subsequent inhibitory influence of the neurogenic genes. Moreover, DER and Htl are differentially involved in the specification of particular progenitors. We conclude that distinct cellular identity codes are generated by the combinatorial activities of Wg, Dpp, EGF, and FGF signals in the progressive determination of embryonic mesodermal cells.