D'Souza, Deana; (1999) Anatomy and development of tendons in vertebrate limbs. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The gross and microscopical anatomy of developing tendons in chick limbs is described. Expression patterns of genes encoding EphA4, a tyrosine kinase receptor involved in direct cell-cell signalling, Six-1, a transcription factor, and Follistatin, a TGF-β antagonist, are documented in developing chick tendons. EphA4 expression is compared with tenascin and collagen I expression. Follistatin applied ectopically to chick limbs inhibits tendon development suggesting a role for TGF-β signalling. Manipulations on chick limbs are carried out to examine co-ordination of tendon and cartilage development. Manipulations that invoke ectopic cartilage lead to ectopic tendons expressing both Follistatin and EphA4 while manipulations that invoke cartilage truncation lead to loss of tendons and expression. Ectodermal signalling is known to control dorso-ventral limb pattern including tendons. EphA4 is expressed in both dorsal and ventral tendons but the former are flattened while the latter round. In limbs of transgenic mice in which Wnt-7a, a dorsalising signal produced by dorsal ectoderm, had been functionally inactivated, the EphA4 expression pattern is ventralised early in dorsal tendon development. In chickens in which Lmx-1, a transcription factor expressed in dorsal mesenchyme in response to Wnt-7a signalling, is ectopically expressed ventrally, no early changes in EphA4 expression pattern in ventral tendons could be detected. However, later, established tendons in ventral regions come to resemble dorsal tendon and double nails form. Spatial and temporal expression patterns of Wnt-7a and Lmx-1 were examined and compared with EphA4 expression in tendons. These analyses suggest that dorso-ventral patterning and specification of tendons involves complex series of parallel interactions between tendon-forming cells and both ectoderm and mesenchyme. A polydactylous human foot with double nails is dissected and the toes identified by the tendons. The anatomy is interpreted from a developmental viewpoint.

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