Disparate Igf1 Expression and Growth in the Fore- and Hind Limbs of a Marsupial Mammal (Monodelphis domestica)

Proper regulation of growth is essential to all stages of life, from development of the egg into an embryo to the maintenance of normal cell cycle progression in adults. However, despite growth's importance to basic biology and health, little is known about how mammalian growth is regulated. In this study, we investigated the molecular basis of the highly disparate growth of opossum fore- and hind limbs in utero. We first used a novel, opossum-specific microarray to identify several growth-related genes that are differentially expressed in opossum fore- and hind limbs of comparable developmental stages. These genes included Igf1. Given Igf1's role in the growth of other systems, we further investigated the role of Igf1 in opossum limb growth. Supporting the microarray results, RT-PCR indicated that Igf1 levels are approximately two times higher in opossum fore- than hind limbs. Consistent with this, while Igf1 transcripts were readily detectable in opossum forelimbs using whole-mount in situ hybridization, they were not detectable in opossum hind limbs. Furthermore, opossum limbs treated with exogenous Igf1 protein experienced significantly greater cellular proliferation and growth than control limbs in vitro. Taken together, results suggest that the differential expression of Igf1 in developing opossum limbs contributes to their divergent rate of growth, and the unique limb phenotype of opossum newborns. This study establishes the opossum limb as a new mammalian model system for study of organ growth.