Biology subjects

Gutierrez, H. L.

Publications and source records attributed to Gutierrez, H. L..

2 recordsLinked to original sources

bioRxiv2019

Interspecies transcriptome analyses identify genes that control the development and evolution of limb skeletal proportion

Despite the great diversity of vertebrate limb proportion and our deep understanding of the genetic mechanisms that drive skeletal elongation, little is known about how individual bones reach different lengths in any species. Here, we directly compare the transcriptomes of homologous growth cartilages of the mouse (Mus musculus) and bipedal jerboa (Jaculus jaculus), which has extremely long metatarsals of the feet and mouse-like arms. When we intersected gene expression differences in metatarsals of the two species with expression differences in forearms, we found that about 10% of all orthologous genes are associated with disproportionate elongation of jerboa feet. Among these, Shox2, has gained expression in jerboa metatarsals where it is not expressed in other vertebrates that have been assessed. This transcription factor is necessary for proximal limb elongation, and we show that it is sufficient to increase mouse distal limb length. Unexpectedly, we also found evidence that jerboa foot elongation occurs in part by releasing latent growth potential that is repressed in mouse feet. In jerboa metatarsals, we observed higher expression of Crabp1, an antagonist of growth inhibitory retinoic acid, lower expression of Gdf10, an inhibitory TGF{beta} ligand, and lower expression of Mab21L2, a BMP signaling inhibitor that we show is sufficient to reduce limb bone elongation. By intersecting our data with prior expression analyses in other systems, we identify mechanisms that may both establish limb proportion during development and diversify proportion during evolution. The genes we identified here therefore provide a framework to understand the modular genetic control of skeletal growth and the remarkable malleability of vertebrate limb proportion.

developmental biology↗

bioRxiv2019

Convergent metatarsal fusion in jerboas and chickens is mediated by similarities and differences in the patterns of osteoblast and osteoclast activities

The extraordinary malleability of the vertebrate limb supports a variety of locomotor functions including running and leaping in cursorial and saltatorial species. In many of these animals, the metatarsals and/or metacarpals are disproportionately elongated to increase stride length and fused into a single larger element, likely to resist fracture due to increased ground reaction forces. Despite the fact that metapodial fusion evolved convergently in modern birds, ungulates, and jerboas, the developmental basis has only been explored in chickens, which diverged from the mammalian lineage approximately 300 million years ago. Here, we use the lesser Egyptian jerboa, Jaculus jaculus, to understand the cellular processes that unite three distinct metatarsal elements into a single cannon bone in a mammal, and we revisit the developing chicken to assess similarities and differences in the localization of osteoblast and osteoclast activities. In both species, adjacent metatarsals align along flat surfaces, osteoblasts cross the periosteal membrane to unite the three elements in a single circumference, and osteoclasts resorb bone at the interfaces leaving a single marrow cavity. However, although spatial and temporal partitioning of osteoblast and osteoclast activities reshape three bones into one in both species, the localization of osteoclasts is distinct. While osteoclasts are uniformly distributed throughout the endosteum of chicken metatarsals, these catabolic cells are highly localized to resorb bone at the interfaces of neighboring jerboa metatarsals. Each species therefore provides an opportunity to better understand the mechanisms that partition osteoblasts and osteoclasts to alter the shape of bone during development and evolution.

evolutionary biology↗