Martin P
Department of Human Anatomy, Oxford University, United Kingdom.
Int J Dev Biol. 1990 Sep;34(3):323-36.
The developing mouse fore- and hindlimbs begin as bumps on the flank of the embryo and grow out to form miniature models of the adult limb during a five day period from E9.5 to E14.5. In this paper I show a series of embryos taken at half-day intervals during limb development and outline the timetable of patterning for each of the component tissues of a limb: epidermis, connective tissues, muscle, nerves and blood vessels. Scanning electron micrographs, supplemented by histological sections, are presented to define a set of standard stages for the description of mouse limb development. I discuss my observations of the mouse limb in the light of current theories of vertebrate limb development, which are based on classic manipulation experiments in the chick as well as more recent molecular data from the mouse system. The limb skeletal pattern in a mouse is laid down in a proximodistal direction, as it is in a bird: the E11.5 forelimb reveals the first signs of a humerus and by E14.5 even the most distal phalanges of the hand are formed. At this late stage ossification sleeves are seen around the proximal limb elements as the cartilage template begins to be converted to a bony skeleton. Myogenic cells stainable with the MF20 antibody against early muscle myosin heavy chain are first seen in the mouse forelimb at E11.5, which is also when the first nerve fascicles begin to enter the limb. From E11.5 to E14.5 both muscle and nerve patterns mature to give distinct muscles at all proximodistal levels of the limb, each muscle with its own nerve branch, and a cutaneous nerve plexus that extends to the fingertips. The developing skin of the mouse limb matures from a bi-layered epidermis overlying an avascular, but otherwise nondescript, prospective dermal layer of mesenchyme at E9.5, to a 4- or 5-layered epidermis with early hair placodes and the first signs of a distinct dermal layer at E14.5. Notable differences between mouse and chick limb development lie in the relatively late formation of the apical ectodermal ridge in the mouse and its unexpectedly close relations with blood vessels, in the absence of anterior and posterior necrotic zones and, possibly, in a late migration of myogenic cells into the mouse limb bud.
发育中的小鼠前肢和后肢最初是胚胎侧面的小肿块，在从E9.5到E14.5的五天时间里逐渐生长，形成成年肢体的微型模型。在本文中，我展示了一系列在肢体发育过程中每隔半天拍摄的胚胎，并概述了肢体各组成组织（表皮、结缔组织、肌肉、神经和血管）的模式形成时间表。文中呈现了扫描电子显微镜照片，并辅以组织学切片，以定义一组用于描述小鼠肢体发育的标准阶段。我根据当前脊椎动物肢体发育理论来讨论我对小鼠肢体的观察结果，这些理论基于对鸡的经典操作实验以及来自小鼠系统的最新分子数据。小鼠的肢体骨骼模式是从近端到远端形成的，就像在鸟类中一样：E11.5的前肢显示出肱骨的最初迹象，到E14.5时，甚至手部最远端的指骨都已形成。在这个后期阶段，随着软骨模板开始转化为骨骨骼，在近端肢体元件周围可以看到骨化套。用针对早期肌肉肌球蛋白重链的MF20抗体可染色的成肌细胞在E11.5首次出现在小鼠前肢，此时也是第一批神经束开始进入肢体的时候。从E11.5到E14.5，肌肉和神经模式都逐渐成熟，在肢体的所有近端到远端水平上形成了不同的肌肉，每块肌肉都有自己的神经分支，以及一个延伸到指尖的皮神经丛。小鼠肢体发育中的皮肤从E9.5时覆盖在无血管但其他方面无明显特征的间充质预期真皮层上的双层表皮，发育到E14.5时具有早期毛基板和明显真皮层最初迹象的4层或5层表皮。小鼠和鸡肢体发育之间的显著差异在于小鼠顶端外胚层嵴形成相对较晚，以及它与血管意外紧密的关系，不存在前后坏死区，并且可能在于成肌细胞向小鼠肢体芽的晚期迁移。
