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Presenting Author(s) Baljinder Mankoo
Abstract Title Meox2 regulates limb muscle morphogenesis.
Full author List Tania Kapoor 1, Petr Valasek 2, Baljinder Mankoo 1*
Text of abstract

The muscles of limbs of vertebrates originate in progenitor cells in the dermomyotome of somites. At the level of the developing limb buds, the lateral dermomyotome undergoes de-epithelialisation to release individual migratory muscle precursor cells that invade the limb bud mesenchyme, where they continue to proliferate and accumulate in two aggregates: the dorsal and ventral muscle masses. These masses are sub-divided along the proximo-distal axis to follow the division of the limb into a stylopod, zeugopod and autopod. Each muscle mass eventually splits to form individual and anatomically distinct muscles.

The mechanism by which the elaborate pattern of the limb musculature is obtained is not well understood. There is evidence that the muscle precursors cells are not autonomously pre-specified, and most experiments using the chick embryo, indicate that it is the limb bud mesoderm that determines the pattern of muscles. However, recently there has been evidence to suggest that in fact migratory muscle precursors do have intrinsic propreties that regulate their

The Meox2 homeobox gene is expressed in migrating limb myoblasts (Fig 1), although it's expression is down regulated as soon as terminal differentiation is initiated. Interestingly, there is a domain of expression in the limb mesoderm that does not correspond to myogenic cells. This is shown by the fact that in Splotch mutant embryos, which have a mutation in the Pax3 gene, myoblasts fail to migrate into the limb bud, there is a persistent expression of Meox2. In fact, at E13.5 there is strong expression of Meox2 in the developing tendons of the digits and other mesoderm.

We have generated null mutations in the murine Meox2 homeobox gene. These mice present a specific and reproducible phenotype affecting the patterning of the limb musculature (Mankoo et al. 1999). Specific muscles are missing (Fig2) and others form ectopically in locations that otherwise would not have muscles (data not shown). We have been trying to decipher the phenotype, to determine whether the defect in limb musculature is due to aberrant differentiation of muscle and/or tendon/connective tissue. Our initial observation that Myf5 gene expression is retarded in limb myoblasts in the absence of Meox2 gene function, suggested an intrinsic defect in the myogenic cells underlies the patterning defects (Mankoo et al. 1999). We have extended the analysis further to investigate whether the there is aberrant expression in limb mesoderm derivatives that contribute to the tendons/connective tissue.
Which session is your work most relevant to: Tissue differentiation