Introduction

For Lindsay and Jeremiah, today is the big day. Lindsay is four months pregnant, and she and her husband will drive to the obstetrician’s office in Lexington, Kentucky, gather in the sonogram room, and take the first low-resolution look at their developing child in the monitor.

"Oh, my goodness, look at that," said Lindsay.

"Take a look at that little face," Jeremiah said.

As memorable as this moment is for tens of thousands of couples each year, few know how that face in the monitor came to be. This remarkable feat of vertebrate biology begins in the first weeks of pregnancy when short lived fetal cells called neural crest cells appear at the upper ridges, or crest, of the embryo’s developing neural tube, the u-shaped precursor of the central nervous system. Some of the cells soon detach from the neural tube and, like salmon spawning upriver, disperse into the pharyngeal arches, the curved columns of fetal ectoderm near the primitive mouth. There, they form a series of bud-like colonies that, in communication with adjacent branchial ectoderm, produce a highly specialized work force of derivative cells that manufacture bone, cartilage, ligament, nerve, and soft tissue that Lindsay and Jeremiah see on the sonogram as their baby’s head.

But if Lindsay and Jeremiah were to spend an hour on Medline, they would soon discover that craniofacial development remains poorly understood. On the molecular level that nature works to build the baby’s head, understanding of the needed "parts list" of genes and proteins that drive the process remains fairly rudimentary. Neither are the cellular dynamics of the process well defined from start to finish. This includes the communal crosstalk among dividing cells that prompt them to branch, arch, and synchronize their self assembly into intricate, three-dimensional patterns as dissimilar as a salivary gland and the temporal bone of the cranium. On a macro level, it also includes profound developmental questions such as: Why does each tissue, bone, and orifice of the human face form in exactly the right place? How do they orchestrate their three-dimensional growth and then integrate seamlessly into a single composite structure that is the human head? Then, of course, there is one of the greatest of all evolutionary mysteries: Why do only vertebrates, from fish to human, have neural crest cells and thus the ability to produce a head?

In years past, these and other related issues were for technical reasons mostly out of scientific reach. But with the arrival of more powerful analytical tools in the research laboratory, scientists have begun to harvest large amounts of biological information and fill in some of the gaps in our understanding. As more data accrue each week in journals and online databases, researchers find themselves fast approaching the now scientifically viable challenge of assembling a more quantitative model of craniofacial development. Or, in lay terms, learning in greater detail how nature constructs the human face.

On the occasion of its 60th anniversary, the NIDCR looks to the future and the likelihood of a more systematic model of craniofacial development. The pages that follow offer the perspectives of several NIDCR researchers and grantees on the scientific road ahead to meet this challenge. They also portray some of the likely benefits of this research to the Nation’s public health. These include a detailed picture of where the molecular glitches might arise in the system, for example, to cleft a lip, omit a tooth bud, or malform a bone. By knowing the most frequent problem spots and, more generally, how healthy craniofacial structures are made, scientists will be in a much better position in the years ahead to dispense molecular medicine and repair more naturally a congenital problem or heal a diseased tissue. They also will be more attuned to the early molecular warning signs of developing disease. This will allow earlier and more accurate diagnoses to correct problems before they become advanced, chronic, and destructive.

As part of this glimpse forward, the NIDCR highlights related areas of dental and oral research that hold tremendous promise. These include studies of head and neck cancer, the development of saliva as a diagnostic fluid, more effective control of orofacial pain, and ongoing hands-on efforts in communities across the nation to help translate the fruits of our science into improved healthcare.

To tell these stories involves a new language of discovery. These include more familiar terms such as genomics, or the study of genes across species, and proteomics, the companion term for proteins. It also includes more recently minted biological pursuits such as the interactome, the complete set of possible protein interactions within a cell, and the microbiome, the complete set of micro-organisms that inhabit distinct parts of the body, such as the mouth, and greatly influence our health and susceptibility to disease over time.

These and other terms represent the need for conceptual distinctions in science. While organizationally helpful, they are in many ways artificial. All human biology is one, from head to toe. As NIDCR supported research unfolds in the years ahead, its lessons will have broad applications throughout science and, more importantly, in hospitals, clinics, and dental offices across the land.

One final note. Although the scientists highlighted in this series are all outstanding, they represent just a cross section of a much larger community of NIDCR researchers and grantees that is making important contributions to their fields and the Nation’s public health.

Next: Neural Crest Cells: The First Mystery of Craniofacial Development