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小鼠肢体早期发育过程中Lhx9基因的表达需要FGF信号通路。

Lhx9 gene expression during early limb development in mice requires the FGF signalling pathway.

作者信息

Yang Yisheng, Wilson Megan J

机构信息

Developmental Biology and Genomics Laboratory, Department of Anatomy, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.

Developmental Biology and Genomics Laboratory, Department of Anatomy, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.

出版信息

Gene Expr Patterns. 2015 Sep-Nov;19(1-2):45-51. doi: 10.1016/j.gep.2015.07.002. Epub 2015 Jul 26.

Abstract

Lhx9 is a member of the LIM-homeodomain gene family necessary for the correct development of many organs including gonads, limbs, heart and the nervous system. In the context of limb development, Lhx9 has been implicated as an integrator for Fibroblast growth factor (FGF) and Sonic hedgehog (Shh) signalling required for proximal-distal (PD) and anterior-posterior (AP) development of the limb. Three splice variants of the Lhx9 transcript are expressed during development, two of which are predicted to act in a dominant negative fashion, competing with the DNA binding version of Lhx9 for binding to cofactors via the LIM-domain. We examined the expression pattern for the three alternative splice forms of Lhx9; Lhx9α, Lhx9β and Lhx9c during early limb development. We have found that of the three Lhx9 isoforms, only Lhx9α and Lhx9c (intact homeodomain) are expressed during early limb development, each with their own distinct expression pattern. Additionally we determined that Lhx9 expression overlaps with FGF10 expression in the developing limb bud mesenchyme. Limb bud explant cultures, in the presence of signalling pathway inhibitors, also indicated that Lhx9 mRNA expression in the limb bud was dependent on FGF signalling.

摘要

Lhx9是LIM同源域基因家族的成员,对包括性腺、四肢、心脏和神经系统在内的许多器官的正常发育至关重要。在四肢发育过程中,Lhx9被认为是成纤维细胞生长因子(FGF)和音猬因子(Shh)信号传导的整合因子,这两种信号对于四肢的近端-远端(PD)和前后(AP)发育是必需的。Lhx9转录本的三种剪接变体在发育过程中表达,其中两种预计以显性负性方式起作用,通过LIM结构域与Lhx9的DNA结合形式竞争与辅因子的结合。我们研究了Lhx9的三种可变剪接形式;Lhx9α、Lhx9β和Lhx9c在四肢早期发育过程中的表达模式。我们发现,在三种Lhx9同工型中,只有Lhx9α和Lhx9c(完整的同源域)在四肢早期发育过程中表达,每种都有其独特的表达模式。此外,我们确定Lhx9的表达与发育中的肢芽间充质中的FGF10表达重叠。在存在信号通路抑制剂的情况下进行的肢芽外植体培养也表明,肢芽中Lhx9 mRNA的表达依赖于FGF信号传导。

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