Crowe R, Henrique D, Ish-Horowicz D, Niswander L
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Development. 1998 Feb;125(4):767-75. doi: 10.1242/dev.125.4.767.
Chick embryonic feather buds arise in a distinct spatial and temporal pattern. Although many genes are implicated in the growth and differentiation of the feather buds, little is known about how the discrete pattern of the feather array is formed and which gene products may be involved. Possible candidates include Notch and its ligands, Delta and Serrate, as they play a role in numerous cell fate decisions in many organisms. Here we show that Notch-1 and Notch-2 mRNAs are expressed in the skin in a localized pattern prior to feather bud initiation. In the early stages of feather bud development, Delta-1 and Notch-1 are localized to the forming buds while Notch-2 expression is excluded from the bud. Thus, Notch and Delta-1 are expressed at the correct time and place to be players in the formation of the feather pattern. Once the initial buds form, expression of Notch and its ligands is observed within each bud. Notch-1 and -2 and Serrate-1 and -2 are expressed throughout the growth and differentiation of the feathers whereas Delta-1 transcripts are downregulated. We have also misexpressed chick Delta-1 using a replication competent retrovirus. This results in induction of Notch-1 and-2 and a loss of feather buds from the embryo in either large or small patches. In large regions of Delta-1 misexpression, feathers are lost throughout the infected area. In contrast, in small regions of misexpression, Delta-1 expressing cells differentiate into feather buds more quickly than normal and inhibit their neighbors from accepting a feather fate. We propose a dual role for Delta-1 in promoting feather bud development and in lateral inhibition. These results implicate the Notch/Delta receptor ligand pair in the formation of the feather array.
鸡胚羽毛芽以独特的时空模式出现。尽管许多基因与羽毛芽的生长和分化有关，但对于羽毛排列的离散模式是如何形成的以及哪些基因产物可能参与其中，我们知之甚少。可能的候选基因包括Notch及其配体Delta和锯齿蛋白，因为它们在许多生物体的众多细胞命运决定中发挥作用。在这里，我们表明，在羽毛芽起始之前，Notch-1和Notch-2 mRNA在皮肤中以局部模式表达。在羽毛芽发育的早期阶段，Delta-1和Notch-1定位于正在形成的芽中，而Notch-2的表达则被排除在芽外。因此，Notch和Delta-1在正确的时间和地点表达，从而参与羽毛模式的形成。一旦最初的芽形成，在每个芽中都能观察到Notch及其配体的表达。Notch-1和-2以及锯齿蛋白-1和-2在羽毛的整个生长和分化过程中都有表达，而Delta-1转录本则被下调。我们还使用具有复制能力的逆转录病毒错误表达了鸡Delta-1。这导致Notch-1和-2的诱导，并且胚胎中大片或小片区域的羽毛芽缺失。在Delta-1错误表达的大片区域，整个感染区域的羽毛都缺失了。相反，在错误表达的小片区域，表达Delta-1的细胞比正常情况更快地分化为羽毛芽，并抑制其邻近细胞接受羽毛命运。我们提出Delta-1在促进羽毛芽发育和侧向抑制中具有双重作用。这些结果表明Notch/Delta受体配体对参与了羽毛排列的形成。
