Knockdown of slit signaling during limb development leads to a reduction in humerus length

被引:7
作者
Rafipay, Alexandra [1 ]
Dun, Xin-Peng [2 ]
Parkinson, David B. [2 ]
Erskine, Lynda [1 ]
Vargesson, Neil [1 ]
机构
[1] Univ Aberdeen, Sch Med Med Sci & Nutr, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
[2] Univ Plymouth, Fac Hlth, Peninsula Med Sch, Plymouth, Devon, England
基金
英国生物技术与生命科学研究理事会;
关键词
bone development; chicken; forelimb; gene expression; Hindlimb; mouse; mouse knockout; Robo; slit; GENOME-WIDE ASSOCIATION; EXPRESSION PATTERNS; VERTEBRATE SLIT; MICE LACKING; CELL FATE; ROBO; MIDLINE; ANGIOGENESIS; RECEPTOR; FAMILY;
D O I
10.1002/dvdy.284
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Background: Slits (1-3) and their Robo (1-3) receptors play multiple non-neuronal roles in development, including in development of muscle, heart and mammary gland. Previous work has demonstrated expression of Slit and Robo family members during limb development, where their functions are unclear. Results: In situ hybridisation confirmed strong expression of Slit2, Slit3, Robo1, and Robo2 throughout mouse limb and joint development. No expression of Slit1 or Robo3 was detected. Analysis of Slit1/2 or Slit3 knockout mice revealed normal limb development. In contrast, locally blocking Slit signaling though grafting of cells expressing a dominant-negative Robo2 construct in the proximo-central region of developing chicken limb buds caused significant shortening of the humerus. Conclusions:These findings demonstrate an essential role for Slit/Robo signaling in regulating bone length during chicken limb development.
引用
收藏
页码:1340 / 1357
页数:18
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