Analysis of Mlc‐lacZ Met mutants highlights the essential function of Met for migratory precursors of hypaxial muscles and reveals a role for Met in the development of hyoid arch‐derived facial muscles

Abstract

The Pax3 and c-met genes are necessary for the development of tongue, diaphragm, and limb muscles. These hypaxial muscles derive from precursors that migrate out of the ventrolateral lip of the somites at occipital, cervical, and limb levels. In this work, we re-examined primary myogenesis in c-met signaling mutants using a skeletal muscle-specific lacZ transgene (Mlc3f-nlacZ-2E). This strategy allowed us to identify precisely the shoulder, limb, tongue, and dermal muscles that need Met for development and to confirm that the morphological structure of epaxial and body wall muscles was normal, even in the most severe c-met mutant. Surprisingly, however, X-gal staining showed that, in this mutant, hyoid arch-derived facial muscles were either reduced or absent, thus revealing that Met also contributes to the development of muscles in the head. Developmental Dynamics 231:582-591, 2004.

Pool-Specific Regulation of Motor Neuron Survival by Neurotrophic Support

“…Notably, we found that in contrast to cutaneous maximus axons, which are severely affected at E12.5, the mpn, which contains C8 -T1 axons projecting toward both the pectoralis minor and pectoralis major muscles, was unaffected at the same stage in both the conditional Nes-Met fl/d and the met d/d loss-of-function mutants (Fig. 4 D), even though both muscles were reported to be missing in the latter mutants (Prunotto et al, 2004). Furthermore, analysis of the pectoralis minor muscle at E15.5 revealed similar innervation pattern between Nes-Met fl/d and control embryos (Fig.…”

The differentiation and morphogenesis of craniofacial muscles

“…In transgenic mice lacking the c-Met receptor, which is necessary for hypoglossal cord formation and extension (Prunotto et al, 2004), some proximal tongue muscles are nonetheless present. This raises the possibility that other tongue myogenic populations may be present in mammals.…”

“…In these contexts, however, HGF acts as a chemoattractant for outgrowing motor axons (Irving et al, 2002). C-Met loss-of-function studies reveal a key role for this signaling pathway in the formation of the muscles of facial expression, e.g., the orbicularis, buccinator, and platysma (Prunotto et al, 2004), in addition to most (but not all) tongue muscles. Neither the mode of action of HGF nor the actual cellular activities by which facial myoblasts disperse from the second branchial arch are known.…”

A Major Reason to Study Muscle Anatomy: Myology as a Tool for Evolutionary, Developmental, and Systematic Biology

“…There are, however, exceptions to the model proposed by Köntges and Lumsden [44]. For example, some mammalian facial muscles that are derived from the second (hyoid) arch and which are apparently associated with connective tissue/fascia also derived from this arch, move into midfacial and jaw territories populated only by frontonasal and first arch crest cells [47][48][49][50][51][52][53] have shown that these facial muscles behave, in terms of C-met mutations, as hypaxial migratory muscles. Contrary to most other head muscles, with the exception of the hypobranchial muscles [46] the facial muscles are absent in organisms with C-met mutations, thus suggesting that during 'normal' ontogeny these mammalian muscles migrate far away from their primary origin.…”