The Kusumi Lab investigates how developmental mechanisms evolve. In particular, the generation of vertebral column varies widely across vertebrate species. Recent advances in molecular biology have revealed that gene regulatory networks play a vital role in shaping developmental processes. The networks that shape the embryonic somites (paired blocks of mesoderm along the future spine), are collectively called the “segmentation clock.”  By comparing the genetics behind musculoskeletal development across multiple classes, we hope to gain insight into how developmental mechanisms evolve. Below is a picture of the somites, which are condensed balls of mesoderm along the future spine.


Surprisingly, the “segmentation clock,” has a unique combination of genes for each vertebrate species investigated so far. Despite major differences in the developmental mechanism, somitogenesis produces a similar product: the vertebral column. Currently we are comparing development in mouse, chick, lizard, frog, turtle, alligator, salamander and snake. The Kusumi Lab recently published an article entitled, “A large-scale view of the evolution of amniote development” that explores the evolution of the molecular and genetic components of the segmentation clock. By studying the genetic components of the segmentation clock, we can learn more about how developmental processes result in morphological evolution, as well as pathology (like scoliosis).


The skeletal elements of the spine, the vertebrae, ribs, sacrum, and occiput, are shaped early in development by the production of embryonic clusters of mesoderm called somites.  Somitogenesis, or the repeated process of somite formation, is coordinated by the Notch, Wnt, and FGF signaling pathways, and investigation has revealed much about the regulatory mechanisms. Human genetic studies, including those from our group, have shown that mutations in Notch pathway genes lead to severe congenital vertebral and rib defects similar to those observed in spondylocostal dysostosis and may underlie other skeletal disorders and syndromes such as congenital scoliosis, caudal agenesis, Klippel-Feil anomaly, VATER and VACTERL syndromes and potentially idiopathic scoliosis.


We have helped to establish the International Consortium for Vertebral Anomalies and Scoliosis, a group of geneticists and orthopaedic surgeons interested in identifying the developmental origins of spinal birth defects. Our collaborative aim is to identify the genetic etiology of human vertebral disorders, including congenital scoliosis, Klippel-Feil syndrome, Jarcho-Levin syndrome, and caudal agenesis. We have developed a unique clinical database of congenital vertebral defect cases for molecular analysis, to aid us in our goal of finding the genetic and developmental causes of spinal birth defects.