Snapshots in NICHD Science 1962–2012: Early Development

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NICHD research in developmental biology seeks to understand normative development, which provides the basis for uncovering the earliest origins of many diseases and conditions, and offers unique opportunities to identify ways of preserving health and preventing or ameliorating disease.

After discovering and sequencing epidermal growth factor (EGF), a protein that stimulates growth of epithelial and other cells and enhances certain cellular pathways, Nobel Prize-winner Stanley Cohen and his colleagues identify EGF's target receptor and mechanism of action. These breakthroughs reveal how signals get into a cell, how malignancy starts, and possible targets for chemotherapy, cellular regeneration, and other interventions.

Researchers prevent the cognitive effects of prenatal alcohol exposure in a mouse model using a neurotrophic peptide treatment. The data suggest a role for these substances in preventing neurodevelopmental anomalies and learning deficits, such as those common in fetal alcohol syndrome.

Building on pivotal findings from Nobel Prize-winner Edward Lewis, who identified homeotic genes and their role in controlling body patterning in Drosophila melanogaster, Nobel Prize-winning researchers Eric Wieschaus and Christiane Nüsslein-Volhard identify additional embryonic control genes and establish that these genes can be classified into functional groups. The findings reveal that these genes are conserved across the animal kingdom and provide important insights into early stages of development and the causes of structural birth defects.

Working with mice, a research team pinpoints reserves of adult stem cells that can generate new bone using a previously unknown type of bone material layering. This finding represents an important step in the effort to use bone stem cells to repair lost or damaged bone.

Building on a theoretical foundation published in 1969 by Eric Davidson and Roy Britten, scientists begin to decipher the intricate sequences of genetic control switches and interacting mechanisms of gene regulatory networks that guide formation of the embryo. Their research fundamentally transforms the way we view developmental processes.

Working with the worm <em>Caenorhabditis elegans</em>, Nobel Prize-winning researchers Andrew Fire and Craig Mello discover that double-stranded RNA triggers a process that suppresses gene activity, revealing a new mechanism of gene regulation.

In their efforts to understand early brain structure, researchers find that the hippocampus, the part of the brain involved with attention and memory, develops differently from the rest of the brain. Unlike most cells in the brain that form close to where they will reside, interneurons–cells that limit the transmission of impulses to regulate communication between networks of brain cells–are born at sites far from the hippocampus and migrate a considerable distance during maturation. Understanding the mechanisms that disrupt the normal migration of these interneurons may reveal the mechanisms underlying disorders such as autism, epilepsy, and schizophrenia that may be related to problems in the hippocampus.

The discovery of the Sonic Hedgehog (<em>Shh</em>) gene in vertebrates and its action in activating homeobox genes, which play a primary role in directing the growth and development of all animals from worms to humans, profoundly changes our understanding of early embryonic development. The finding also exposes how body polarity (head end versus tail end) is established and how limbs and parts of the central nervous system are formed.

Collaborative research between basic scientists and clinical investigators identifies a mutation in the <em>CCDC40</em> gene that causes abnormalities in motile cilia function. This function is important in early developmental processes and later organ function, such as clearing mucus from the lungs and other parts of the respiratory system.

Researchers find that inhibiting dopamine signaling in zebrafish, as in humans, reduces movement, paving the way to screen for compounds that improve swimming in zebrafish models of Parkinson's disease.

By creating an experimental mouse model for Down syndrome, the Ts65Dn mouse, scientists have a valuable tool for identifying factors that can prevent or reduce the intellectual and other problems associated with the syndrome and with other conditions.

Looking to the Future

As we look to the future, we aim to develop knowledge and tools to predict or prevent a range of human structural and functional variations and to better understand the developmental origins of health and disease.