Department of Organ Formation, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan.
Biochem Biophys Res Commun. 2010 Jan 22;391(4):1653-7. doi: 10.1016/j.bbrc.2009.12.109. Epub 2009 Dec 30.
Digit and interdigit (D/ID) development is one of the important research fields in molecular developmental biology. Interdigital cell death (ICD) is a morphogenetic event which has been considered as an essential process for D/ID formation. Although some growth factors including Bmp and Fgf signaling can modulate ICD, growth factor crosstalk regulating ICD is poorly understood. Wnt canonical pathway and Bmp signal crosstalk has been considered as the essential growth factor crosstalk in organogenesis. To elucidate the crosstalk to regulate the D/ID formation, we analyzed conditional mutant mice with limb bud ectoderm expressing constitutively activated beta-catenin signaling. We showed that modulation of Wnt/beta-catenin signal in the limb ectoderm including the AER regulates ID apoptosis. We also demonstrated that Wnt/beta-catenin signaling in the ectoderm can positively regulate Fgf8 possibly antagonizing the epithelial derived Bmp signaling. Human birth defects for digit abnormalities have been known to be affected by multiple parameters. Elucidation of the potential mechanisms underlying such D/ID development is an urgent medical issue to be solved. This work would be one of the first studies showing essential growth factor cascades in the D/ID formation.
指(趾)间(D/ID)发育是分子发育生物学的重要研究领域之一。指间细胞死亡(ICD)是一个形态发生事件,被认为是 D/ID 形成的必要过程。尽管包括 Bmp 和 Fgf 信号在内的一些生长因子可以调节 ICD,但生长因子串扰调节 ICD 的机制尚不清楚。Wnt 经典途径和 Bmp 信号串扰被认为是器官发生中重要的生长因子串扰。为了阐明调节 D/ID 形成的串扰,我们分析了肢芽外胚层中表达组成型激活β-catenin 信号的条件性突变小鼠。我们表明,肢外胚层中 Wnt/β-catenin 信号的调节(包括 AER)调节 ID 细胞凋亡。我们还证明,外胚层中的 Wnt/β-catenin 信号可以正向调节 Fgf8,可能拮抗上皮衍生的 Bmp 信号。已经知道,人类的手指异常出生缺陷受多种因素的影响。阐明 D/ID 发育的潜在机制是一个亟待解决的医学问题。这项工作将是首次展示 D/ID 形成中关键生长因子级联的研究之一。
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