Identification of members of the Wnt signaling pathway in the embryonic pituitary gland

Identification of members of the Wnt signaling pathway in the embryonic pituitary gland
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DOI:
10.1007/s00335-001-2076-0
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发表时间:
2001-11-01
期刊:
影响因子:
2.5
通讯作者:
Camper, SA
Camper, SA
中科院分区:
生物学4区
文献类型:
--
作者:
Douglas, KR;Brinkmeier, ML;Camper, SA

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Prop 1是对脑垂体发育重要的几种转录因子之一。PROP 1和其他关键垂体转录因子的下游靶点在很大程度上仍然未知。我们已经产生了一个部分表达谱的发育中的垂体含有超过350个成绩单,使用cDNA消减杂交Prop 1(DF/DF)和野生型胚胎垂体原基。在这项研究中鉴定了许多类基因,包括转录因子、膜相关分子和细胞周期调节因子。在转录本中,34%与已知基因没有序列相似性,但与EST相似,4%代表新序列。原位杂交证实了一些克隆的垂体表达。在发育中的垂体中鉴定了Wnt信号通路的几个成员。在开发垂体文库中鉴定了卷曲2受体Ape、β-连环蛋白、groucho和TCF 4的新同种型(正式命名为Tcf 712)。本文报道了三种N-末端可变剪接的Tcf 712亚型,每一种都缺乏DNA结合结构域。功能研究表明这些异构体在某些情况下可以作为Win信号的内源性抑制剂。这是Tcf 712和Fzd 2在发育中垂体中表达的首次报道。这些分子可能在垂体个体发育过程中介导Wnt信号传导中起重要作用。我们希望从这些图书馆的其他成绩单参与脑下垂体的发展。
Prop1 is one of several transcription factors important for the development of the pituitary gland. Downstream targets of PROP1 and other critical pituitary transcription factors remain largely unknown. We have generated a partial expression profile of the developing pituitary gland containing over 350 transcripts, using cDNA subtractive hybridization between Prop1(df/df) and wild-type embryonic pituitary gland primordia. Numerous classes of genes including transcription factors, membrane associated molecules, and cell cycle regulators were identified in this study. Of the transcripts, 34% do not have sequence similarity to known genes, but are similar to ESTs, and 4% represent novel sequences. Pituitary gland expression of a number of clones was verified using in situ hybridization.Several members of the Wnt signaling pathway were identified in the developing pituitary gland. The frizzled2 receptor, Ape, beta -catenin, groucho, and a novel isoform of TCF4 (officially named Tcf712) were identified in developing pituitary libraries. Three N-terminal alternatively spliced Tcf712 isoforms are reported here, each of which lacks a DNA-binding domain. Functional studies indicate that these isoforms can act as endogenous inhibitors of Win signaling in some contexts.This is the first report of Tcf712 and Fzd2 expression in the developing pituitary. These molecules may be important in mediating Wnt signaling during pituitary ontogeny. We expect other transcripts from these libraries to be involved in pituitary gland development.