The Mouse Limb Anatomy Atlas: An interactive 3D tool for studying embryonic limb patterning

To improve the resources available in the mouse model, we have generated a free, web-based, interactive reference of limb muscle, tendon, and skeletal structures at embryonic day (E) 14.5 http://www.nimr.mrc.ac.uk/3dlimb/ webcite. The Atlas was generated using mouse forelimb and hindlimb specimens stained using immunohistochemistry to detect muscle and tendon. Limbs were scanned using Optical Projection Tomography (OPT), reconstructed to make 3D models and annotated using computer-assisted segmentation tools in Amira 3D Visualisation software. The annotated dataset is visualised using Java, JAtlasView software. Users click on the names of structures and view their shape, position and relationship with other structures within the 3D model and also in 2D virtual sections.The Mouse Limb Anatomy Atlas provides a novel and valuable tool for researchers studying limb development and can be applied to a range of research areas, including the identification of abnormal limb patterning in transgenic lines and studies of models of congenital limb abnormalities. By using the Atlas for "virtual" dissection, this resource offers an alternative to animal dissection. The techniques we have developed and employed are also applicable to many other model systems and anatomical structures.The mouse is a frequently used model for studying limb development and the anatomical similarities between mouse and human limbs make it an excellent system for understanding human limb defects. An advantage of the mouse model is that many molecular techniques have been established for studying the genetic pathways regulating limb development, so it is possible to link genetic mechanisms with patterning events. Typically, limb patterning is studied using two-dimensional (2D) microscopy of whole mount or histological sections of tissues or embryos. A significant limitation of these approaches is that they do not allow the interpretation of the complex physical relationship between individual limb elem