Schweizer H, Johnson R L, Brand-Saberi B
Institute of Anatomy and Cell Biology, University of Freiburg, Albertstrasse 17, 79104 Freiburg, Germany.
Anat Embryol (Berl). 2004 Apr;208(1):7-18. doi: 10.1007/s00429-003-0373-y. Epub 2004 Mar 6.
Limb buds develop from lateral plate-derived stationary mesenchyme and are invaded by cells from extrinsic regions. The largest populations of these cells are myogenic precursor cells that originate from the lateral dermomyotomes. After detachment under the influence of SF/HGF, myogenic precursor cells migrate in a proximo-distal direction and populate a dorsal and ventral zone. The patterning mechanism leading to the segregation of dorsal and ventral myogenic cells is at present not understood. Lmx1b, a LIM homeodomain transcription factor expressed in the dorsal mesenchyme of the developing limb bud, forms a sharp dorso-ventral boundary of expression within the limb. We have investigated the mechanisms of dorso-ventral patterning of muscle precursor cells in the limb buds with respect to Lmx1b expression using quail-chick chimeras and transgenic mice. Although cells appeared to be capable of migrating either ventrally or dorsally, their migration was restricted to the position they had attained during normal development or in the experimental situation. They were never found to cross the dorso-ventral boundary. Immunohistochemistry and histological analysis of mice carrying a LacZ reporter gene under the control of the endogenous Lmx1b locus confirmed that myogenic precursors in the limb bud were devoid of Lmx1b expression. In addition, it was shown that Lmx1b is not only expressed at early stages of limb development but maintains its pattern, at least until after birth. The present study provides new insights into migratory pathways of myogenic precursor cells and reveals details of Lmx1b expression on a cellular basis within the limb.
肢体芽从侧板衍生的静止间充质发育而来，并被来自外部区域的细胞侵入。这些细胞中数量最多的是源自外侧皮肌节的生肌前体细胞。在SF/HGF的影响下脱离后，生肌前体细胞沿近-远方向迁移，并在背侧和腹侧区域聚集。导致背侧和腹侧生肌细胞分离的模式形成机制目前尚不清楚。Lmx1b是一种在发育中的肢体芽背侧间充质中表达的LIM同源域转录因子，在肢体内形成了一个清晰的背-腹表达边界。我们利用鹌鹑-小鸡嵌合体和转基因小鼠，研究了肢体芽中肌肉前体细胞背-腹模式形成与Lmx1b表达相关的机制。尽管细胞似乎能够向腹侧或背侧迁移，但它们的迁移仅限于在正常发育或实验情况下所到达的位置。从未发现它们穿过背-腹边界。对内源性Lmx1b基因座控制下携带LacZ报告基因的小鼠进行免疫组织化学和组织学分析证实，肢体芽中的生肌前体缺乏Lmx1b表达。此外，研究表明Lmx1b不仅在肢体发育的早期阶段表达，而且至少在出生后仍保持其表达模式。本研究为生肌前体细胞的迁移途径提供了新的见解，并揭示了肢体内细胞水平上Lmx1b表达的细节。
