Developmental Biology

Children's Research Institute and The Medical College of Wisconsin have developed a vigorous and growing program in developmental biology.  The program consists of 22 laboratories studying diverse aspects of embryogenesis and stem cell biology.

What is developmental biology?

Understanding the molecular mechanisms that control how an embryo is formed following fertilization is essential to realize the potential of stem cells as therapies to treat common diseases such as diabetes, hypertension, metabolic disease and even cancer. To discover the processes that cause congenital disease requires a thorough understanding of how tissues and cells formed during gestation. A thorough appreciation of the basics of developmental biology will produce novel treatments and diagnostics that directly impact health care.

During the last 10 years, a concentrated effort has been made by the institute to expand in areas of biomedical research that aim to unravel the fundamental mechanisms through which human beings develop. This has resulted in the recruitment of several leading researchers in the areas of stem cell biology, cardiogenesis, vasculogenesis and hepatogenesis. Recruitment also included specialists in the development of the gastrointestinal tract, kidney, ear, eye and nervous system. This group of internationally renowned scientists and clinicians has attracted extensive funding from the National Institutes of Health and private sources. They have published hundreds of original research articles and have trained dozens of postdoctoral fellows and graduate students.

Elena Semina, PhD, laboratory

This laboratory applies molecular genetic approaches to identify genes that interfere with human development, with the goal of understanding mechanisms of normal and aberrant development and better management of associated human disorders.

Elena Semina, PhD, focuses on the Pitx family of homeodomain-containing transcription factors, which play an important role in the development of multiple organs including the anterior segment of the eye, craniofacial region, brain, heart and umbilical area. The PITX2 gene was identified by positional cloning as a gene involved in Axenfeld-Rieger syndrome, a congenital condition characterized by the anterior segment anomalies with glaucoma and also dental and umbilical defects. The PITX3 gene was found to be responsible for Peters' anomaly/anterior segment dysgenesis phenotype and cataracts in humans and aphakia in mice.

Ocular development in Pitx2- and Pitx3-mutant mice is arrested at the stage of lens vesicle formation and its separation from the corneal ectoderm, which normally induces development of the anterior segment structures. Abnormal development of the anterior segment of the eye often leads to blindness due to glaucoma, corneal opacities or cataracts. The molecular mechanisms responsible for normal development of the anterior segment of the eye are not well defined and studies of Pitx genes' pathways present the unique opportunity to approach these processes. Primary institute efforts are directed toward identification of factors involved in regulation of PITX expression as well as downstream targets genes. The continuing goal is development of animal models of glaucoma and other ocular disorders for in vivo examination of the pathologic processes and genetic identification of secondary factors contributing to disease severity.