肢芽发育过程中 slit 信号的敲低导致肱骨长度减少。

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

机构信息

Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.

Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth, UK.

出版信息

Dev Dyn. 2021 Sep;250(9):1340-1357. doi: 10.1002/dvdy.284. Epub 2021 Jan 16.

DOI:10.1002/dvdy.284

PMID:33347679

Abstract

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.

摘要

背景

缝隙蛋白（1-3）及其 Robo（1-3）受体在发育过程中发挥多种非神经元作用，包括肌肉、心脏和乳腺的发育。先前的研究表明，缝隙蛋白和 Robo 家族成员在肢体发育过程中表达，但其功能尚不清楚。

结果

原位杂交证实 Slit2、Slit3、Robo1 和 Robo2 在小鼠肢体和关节发育过程中均有强烈表达。未检测到 Slit1 或 Robo3 的表达。Slit1/2 或 Slit3 敲除小鼠的分析显示肢体发育正常。相比之下，通过在发育中的鸡肢芽近端-中心区域移植表达显性负性 Robo2 构建体的细胞来局部阻断缝隙信号，导致肱骨显著缩短。