Myf5-/- :MyoD-/- amyogenic fetuses reveal the importance of early contraction and static loading by striated muscle in mouse skeletogenesis.

The mechanical loading of striated muscle is thought to play an important role in shaping bones and joints. Here, we examine skeletogenesis in late embryogenesis (embryonic day 18.5) in Myf5-/-:MyoD-/- fetuses completely lacking striated muscle. The phenotype includes enlarged and fused cervical vertebrae and postural anomalies, some viscerocranial anomalies, long bone truncation and fusion, absent deltoid tuberosity of the humerus, scapular and clavicular hypoplasia, cleft palate, and cleft sternum. In contrast, neurocranial bone development was essentially normal. While the magnitude of individual effects varied throughout the skeletal system, the results are consistent with skeletal development depending on functional muscles. Novel abnormalities in the amyogenic fetuses relative to less severely paralyzed phenotypes extend our understanding of skeletogenic dependence on embryonic muscle contraction and static loading.

Arrested development in Xenopus laevis tadpoles: how size constrains metamorphosis.

Xenopus laevis tadpoles that arrest development and remain as larvae for several years sometimes occur spontaneously in laboratory populations. These tadpoles cease development at an early hindlimb stage, but continue to grow and develop into grossly deformed giants. Giant tadpoles lack thyroid glands, and differ in morphology and behaviour from normal larvae. They are negatively buoyant, typically with small and partially solidified lungs, and have greatly enlarged fat bodies. Giant tadpoles have mature gonads with eggs and sperm, whereas normal tadpoles of the same stage have undifferentiated gonads. Larval reproduction has never been reported in anurans, but gonadal development decoupled from metamorphosis brings these giants the closest of any anurans to being truly neotenic. We discuss behavioural and morphological factors that may hinder both reproduction in giant Xenopus larvae and the evolution of neoteny in anurans in general. Experimental treatment with exogenous thyroid hormone induces some, but not complete, metamorphic changes in these giants. The limbs and head progress through metamorphosis; however, all tadpoles die at the stage when the tail would normally be resorbed. The disproportionate growth of tissues and organs in giant tadpoles may preclude complete metamorphosis, even under exogenous thyroid hormone induction.

Tissue sensitivity to thyroid hormone in athyroid Xenopus laevis larvae.

Tadpoles that spontaneously arrest development and remain as larvae occur occasionally in Xenopus laevis populations. These non-metamorphosing tadpoles continue to grow, and they develop into grossly deformed giant individuals which come as close as any anurans to being truly neotenic. Giant X. laevis tadpoles that fail to metamorphose lack thyroid glands. In this study, the hypothesis that the tissues of these tadpoles nevertheless remain thyroid hormone sensitive was tested, by exposing isolated tadpole tail tips to exogenous thyroid hormone in tissue culture. The tail tips from giant tadpoles significantly shrank in response to the thyroid hormone treatment, showing that their tissue was still capable of metamorphosis. However, the amount of shrinkage was less than that observed in tail tissue from normal tadpoles. It was hypothesized that complete induction of metamorphosis may not be possible in the giant tadpoles due to a disproportionate growth and development of tissues and organs.