Nearly half of all birth defects involve the face and skull, but the causes of these problems remain largely unknown. To better understand—and ultimately prevent—such defects, a new project involving the University of Iowa will focus on creating a first-ever encyclopedic database on how the faces of healthy children develop and what goes wrong to cause defects.

The effort, called FaceBase, is a five-year initiative funded by the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health.

In early October, the NIDCR announced that the UI and the University of Pittsburgh will jointly serve as the FaceBase Management and Coordination Hub. The two coordinating organizations received a shared five-year, $9 million grant. The effort involves a total of 12 sites nationwide, with 10 other grants funding specific projects. The resulting database will be publicly available at no cost to scientists.

Jeff Murray, MD, professor in the UI Carver College of Medicine, as well as colleges of dentistry, liberal arts and sciences, and public health, will be the hub's co-principal investigator along with longtime collaborator Mary Marazita, PhD, professor of oral biology and human genetics and director of the Center for Craniofacial and Dental Genetics at the University of Pittsburgh.

Exciting Challenge

"It's an exciting challenge to help produce a database that brings together biochemical, molecular, genetic and imaging findings related to human facial and skull development," said Murray, who also is a pediatrician with University of Iowa Children's Hospital. "FaceBase will essentially create a 'how-to' manual of all the instructions that are needed to properly develop the mid-face, which includes the nose, upper lip and palate, or roof of the mouth.

"This knowledge can then go a long way to preventing defects such as cleft lip and palate and jaw malformations," added Murray, who has long studied cleft lip and palate, which affects nearly 5 million people worldwide.

In addition to bringing together existing research, FaceBase involves 10 independent research projects, each focused on a specific aspect of craniofacial development.

"Working with the University of Pittsburgh, we will make sure that both existing and new information is integrated and made easily available so that scientists and clinicians worldwide can use it. The effort is the epitome of interdisciplinary research," Murray said.

In the first weeks of pregnancy, bud-like colonies of embryonic cells form near the primitive mouth and, in conjunction with adjacent tissue, produce highly specialized cells. These cells develop into the bone, cartilage, ligament, nerve and soft tissue that are visible as the developing face in the first sonogram of a fetus. However, many questions remain about how this development occurs between the first embryonic cells and the first sonogram.

Parts List

FaceBase aims to include a comprehensive "parts list" of the genes and proteins that drive the embryonic cells, as well step-by-step understandings of cellular dynamics that drive tissue formation, especially the communication among dividing cells that ultimately leads to their synchronized self-assembly into intricate, three-dimensional patterns as dissimilar as a salivary gland and the temporal bone of the skull. Researchers also seek to understand how the tissues and structure of the human face form in exactly the right place.

"It's like exploring the cosmos," Marazita said. "We can see certain things, but we don't know in detail how they became what they are or how they got where they are, and there are additional aspects that are not even visible to us right now.

"Once we have more answers and start putting the information into the FaceBase database, we will understand more. And then eventually, we can do more to intervene when facial development starts to go wrong or prevent defects in the first place."