生物谷报道:近日,美国科学家发现了对手指再生起关键作用的基因——Sonic Hedgehog(SHH),它将可以使伤残、短小手指再生。这一发现具有重大突破意义,人类可以利用最新基因技术拥有额外的一至两根手指,不仅减轻了工作负担,甚至可能还会围绕这多出的手指掀起新的时尚潮流。
人类、鸟类以及其他生物拥有相同的基因组来控制手指、脚趾以及翅膀的生长,然而生物间指头数量与形态差异为何如此之大曾一直困扰着科学家们。近日,美国威斯康星大学麦迪逊分校研究人员们发现SHH基因在决定手指、脚趾形态以及个数过程中起到重要的作用。
他们首先在约翰·法伦实验室对雏鸡做了实验,观察到大量不同基因组织在不同时间发出的综合信号最终形成了手指的生长。随后他们将手指再生部分取名为“指骨形成区域”(phalanx-forming region),在接下来的实验过程中他们又发现,手指或脚趾的再生是通过间叶细胞(mesenchymal cells),而不是过去认为的软骨细胞(cartilage cells),这一发现突破了传统的研究结果。
哈兰·温菲尔德·莫斯曼(Harland Winfield Mossman) 教授多年来一直致力于研究在胚胎生长阶段细胞是如何决定指头、牙齿以及羽毛形态的。他表示,对于鸟类以及哺乳动物来说,拳击手套形状的远端肢体末梢(autopod)会生长出手指,而发育着的脚则长出脚趾,它们由两个相交叉的区域构成。
指线或趾线(digital rays)是由间叶细胞与软骨组织构成的,它将来会形成成年动物脚趾中的指骨或趾骨。而间叶细胞组织组成了手指、脚趾相间的的部分,它们填充了指、趾线的间的空隙,再生也就是由这一部分来完成。
与此同时,许多研究人员认为SHH基因中的其它次级信号中心下游(other secondary signaling centers downstream of SHH)也对手指、脚趾精确特性构成起到关键作用。研究人员肖恩·哈索(Sean Hasso)表示,他们目前正在探究指线中决定手指产生的那部分确切细胞,以及控制手指数量、大小以及形状的分子。通过在胚胎远端肢体末梢(autopod)上进行显微外科以及分子标识等研究工作后,他表示,指线顶端的间叶细胞生长所产生的细胞,最终形成了手指的生长,是确定手指数量、大小和形状的关键所在。
通过实验研究人员得出结论,人们可以通过刺激间叶细胞的生长而产生新的手指。重要的是,此项发现对于那些先天手指缺陷或后天伤残的人们来说,无疑带来许多美好的希望。但是这种最新的技术还需要结果严格的论证才能实现临床治疗。(援引网易探索 和平)
生物谷推荐参考文献:
Published online on March 11, 2008
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0707899105
DEVELOPMENTAL BIOLOGY
Unique SMAD1/5/8 activity at the phalanx-forming region determines digit identity
Takayuki Suzuki*,,, Sean M. Hasso*, and John F. Fallon*,
*Department of Anatomy University of Wisconsin, 1300 University Avenue, Madison, WI 53706; and Department of Developmental Neurobiology, Institute of Development Aging and Cancer (IDAC) Tohoku University, Seiryo-cho 4-1, Aoba-Ward, Sendai-City, Miyagi-Pref 980-8575, Japan
Edited by Clifford J. Tabin, Harvard Medical School, Boston, MA, and approved December 20, 2007 (received for review August 21, 2007)
Abstract
The zone of polarizing activity is the primary signaling center controlling anterior–posterior patterning of the amniote limb bud. The autopodial interdigits (IDs) are secondary signaling centers proposed to determine digit identity by acting on the cells of the digital ray. Here, we focus on events accompanying digital fate determination and define a region of the digital ray that expresses Sox9 and Bmpr1b and is phosphorylated-SMAD1/5/8 (p-SMAD1/5/8) positive. We name this region the phalanx-forming region (PFR), and show that the PFR cells arise from the distal subridge mesenchyme of digital ray. This phalanx-forming cell lineage is subsequently committed to the cartilage lineage; the fate of these cells is initially labile but becomes fixed as they are incorporated into the condensed cartilage of the digit primordium. Using an in vivo reporter assay, we establish that each digital PFR has a unique p-SMAD1/5/8 activity signature. In addition, we show that changes in this activity correlate with the identity of the digit that forms after experimental manipulation, supporting the idea that threshold signaling levels can lead to different developmental outcomes in a morphogenetic field. Our data define the molecular profile of the PFR, and we propose a model for understanding formation and variation of digits during autopodial development.
Bmpr1b | brachydactyly | limb development