Segmental variations in the patterns of somatic muscles: What roles for Hox?

Textbook drawings of human anatomy illustrate the diversity of body muscles that are essential for coordinated movements. The genetic and molecular bases of this muscle diversity remain, however, largely unknown. The rather simple Drosophila larval musculature - every (hemi)-segment of the Drosophila larva contains about 30 different somatic muscles, each composed of a single multinucleate syncitial fibre- makes it an ideal model to study this process ([1]). Each muscle displays its own identity which can be described as its specific position and orientation with respect to the dorso-ventral (D/V) and antero-posterior (A/P) axes, size (number of nuclei), attachment sites to the epidermis and innervations [2]. Muscle specification is a multi-step process. Each muscle is seeded by a founder cell (FC). FCs display the unique property of being able to undergo multiple rounds of fusion with fusion competent myoblasts (FCMs) [3]. The current view is that muscle identity reflects the expression by each FC of a specific combination of "identity" transcription factors (iTFs) (reviews by [4, 5]). The transcriptional identity is propagated from the FC to nuclei of FCM recruited by the growing myofibre during the fusion process [6]. FCs are born from the asymmetric division of progenitor cells which are themselves selected by Notch (N)-mediated lateral inhibition from promuscular clusters (equivalence groups of cells) specified at fixed positions within the somatic mesoderm [7]; see Fig.2). The abdominal (A) A2 to A7 segments of the Drosophila embryo present the same muscle pattern, the thoracic (T) T2-T3 and A1 segments show variations of this pattern and the first thoracic segment (T1) and the eighth abdominal segment (A8) present fewer and more diversified muscles [2]. While it is has long been shown that this diversification of the muscle pattern is determined by the autonomous function of homeotic genes in the mesoderm [9], the step at which segment-specific information carried by Hox proteins is integrated into the muscle specification process remained unknown.