F R O M C E L L S T O S E L V E S

Developmental Biology

Understanding Normal and Abnormal Development

Eunice Kennedy Shriver National Institute of Child Health and Human Development
FROM CELLS TO SELVES 

Developmental Biology: Understanding Normal and Abnormal Development 

Contents
 

The NICHD Mission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
 

The Strategic Planning Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
 

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
 

Scientific Goals of the Strategic Plan. . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
 

Genetic Studies of Birth Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
 

Basic Mechanisms of Normal and Abnormal Development . . . . . . . . . . . . . . . . . . . . 6
 

Development of Model Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
 

Research Technologies and Resources. . . . . . . . . . . . . . . . . . . . . . . . . . 10
 

Functional Genomics and Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
 

Imaging Technology and Visualization of Development Processes . . . . . . . . . . . . . . . 10
 

Developmental Databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
 

Programs for the Study of the Developmental Biology of Birth Defects . . . . . . . . . . . . 11
 

Training and Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
 

Appendix—Roster of Advisors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
 

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FROM CELLS TO SELVES 

Developmental Biology: Understanding Normal and Abnormal Development 

The NICHD Mission
 

The National Institute of Child Health and Human 

Development (NICHD) seeks to ensure that every individual 

is born healthy, is born wanted, and has the opportunity to 

fulfill his or her potential for a productive life unhampered 

by disease or disability. The Institute further strives to help 

parents have the children they want, at the times they want 

them, and to ensure that every mother experiences a 

pregnancy free of adverse complications. Key to the 

success of this mission is answering the fundamental 

questions of how a single fertilized cell eventually develops 

into a fully functional adult human being and how a 

multitude of genetic and environmental factors influence 

that process for good or ill. 

Programs at the NICHD are based on the concepts that 

adult health and well-being are determined in large part 

by episodes early in life, sometimes before birth; that 

human development is continuous throughout life; and that 

optimal outcomes of development are important not only to 

the individual but to society. NICHD research is also 

directed toward restoring or maximizing individual 

potential and functional capacity when disease, injury, or a 

chronic disorder intervenes in the developmental process. 

Thus, the NICHD mission truly spans the life cycle, and 

much of the health and well-being of our population 

depends on the success of the Institute’s research. 

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F R O M C E L L S T O S E L V E S 

Developmental Biology: Understanding Normal and Abnormal Development 

The Strategic Planning Process
 

During 1998 and 1999, the NICHD staff engaged the 

scientific community in jointly developing a strategic plan 

to facilitate achieving its mission. The initial framework 

document for this plan, From Cells to Selves, highlighted 

four areas for immediate strategic development and 

described a series of scientific goals under each area. 

These four areas were as follows: 

• Genetics and Fetal Antecedents of Disease Susceptibility 

includes the interaction of the genotype with 

socioeconomic, environmental, and psychological 

factors in the fetal and postnatal environment that 

contribute to health or the pathophysiology of 

diseases. 

• Reproductive Health for the 21st Century comprises 

the biological and behavioral factors that allow 

couples to have healthy children when they want them 

and the reproduction-related conditions that may 

affect women during and after their reproductive 

years. 

• Developmental Biology: Understanding Normal and 

Abnormal Development consists of the basic biological 

science necessary to understand early development 

in utero and through the time when many organ 

systems form. 

• Biobehavioral Development includes research to better 

understand the developmental processes involved in 

forming cognitive, learning, emotional, social, and 

physical behaviors, and the biological and 

environmental factors that make infants, children, and 

adolescents more susceptible to behavioral disorders 

or to adopting risk-taking and violent behaviors. 

This document refines the goals and objectives outlined 

under the area titled “Developmental Biology: 

Understanding Normal and Abnormal Development.” 

To help establish the more detailed research agenda that 

follows, the NICHD convened a working group 

comprising distinguished scientists (see Appendix) from 

around the country and asked them to collaborate with 

Institute staff to identify and prioritize research goals and 

to suggest appropriate strategies to meet those goals. 

The working group drew upon ongoing planning efforts, 

previous emphasis areas, recent forums, workshops, 

conferences, and research findings to develop a draft of 

the strategic plan that would guide the Institute’s research 

agenda in developmental biology for the next 5 years. 

The draft plan was posted on the NICHD Web site to 

allow members of advocacy groups, nonprofit 

organizations, the scientific community, and the general 

public to comment. In addition, the Institute shared the 

plan with members of the National Advisory Child 

Health and Human Development Council and with the 

Friends of the NICHD, a coalition of more than 100 

professional and patient organizations committed to the 

Institute’s scientific mission. After consolidating and 

reviewing all comments, the NICHD revised and 

finalized the plan. This document is intended as a 

targeted, but flexible, blueprint that can be modified as 

new scientific findings, research opportunities, or 

resources become available. 

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FROM CELLS TO SELVES 

Developmental Biology: Understanding Normal and Abnormal Development 

Introduction
 

Although the Institute has made great progress in 

preventing infant deaths resulting from low birth weight, 

prematurity, respiratory distress syndrome, and Sudden 

Infant Death Syndrome (SIDS), birth defects remain the 

leading cause of deaths in infants younger than 1 year 

of age, accounting for one of five infant deaths. 

Estimates indicate that more than 150,000 babies in the 

United States are born each year with significant birth 

defects (about 4 percent of all live births). Families with 

babies born with severe, nonfatal birth defects, often 

accompanied by mental retardation, are burdened 

financially by expensive special medical treatment, 

education, rehabilitation, and other supportive services 

to care for their disabled children from childhood into 

adulthood. While there are thousands of different types 

of birth defects with varying degrees of severity, the 

lifetime costs to the U.S. economy of children born with 

any of 17 major structural birth defects are estimated to 

be more than $6 billion a year. Consequently, the full 

economic impact for all birth defects is much greater. 

The emotional costs to families are incalculable. 

Developing effective strategies to prevent birth defects is 

possible only with a thorough understanding of the 

epidemiology, etiology, and pathogenesis of birth 

defects–areas where tremendous gaps in knowledge still 

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FROM CELLS TO SELVES 

Developmental Biology: Understanding Normal and Abnormal Development 

exist. Progress in these areas requires a better 

understanding of clinical phenotypes, human syndrome 

delineation, teratogens, epidemiology, and the natural 

history of birth defects. Also essential is gaining an indepth understanding of the basic mechanisms that 

underlie normal developmental processes, through the 

appropriate use of animal models and stem cell* 

research. Accomplishing these goals will require a joint 

effort by clinicians and basic scientists to approach birth 

defects research from their respective strengths and build 

on each other’s progress. Thus, a common theme in the 

emphasis areas outlined in this strategic plan is the need 

for a two-way flow of information between scientists with 

different types of research interests and endeavors. Such 

collaboration will help to fill the gaps in knowledge 

about how both genetic and environmental perturbations 

of normal processes cause developmental abnormalities. 

Findings from clinical studies will also provide insight 

and direction to basic scientists studying developmental 

processes. Similarly, translating basic findings from the 

use of animal models and stem cell research to relevant 

clinical research will increase our understanding of 

human embryonic development and the formation of 

structural birth defects. 

The scientific goals delineated in the following section of 

this strategic plan take advantage of the most recent 

technological and scientific advances and provide a 

schema for the NICHD to continue its efforts to clarify the 

patterns and processes involved in the genetic program 

of human development. In the context of this strategic 

plan, the timeframe of development ranges from the 

earliest stages of embryonic development, including 

blastocyst and trophoblast formation, gastrulation, 

neurulation, and the establishment of the basic body 

plan, through organogenesis. In certain cases, such as 

research dealing with the immune and nervous systems, 

studying later stages of development may help scientists 

to better understand how these systems respond to the 

environment during the postnatal period. 

The sections on Research Technologies and Resources 

and Training and Education address resource and 

training requirements, which the NICHD views to be as 

vital to the advancement of these research areas as is 

support of basic research itself. The section on Research 

Technologies and Resources also capitalizes on and 

further develops the essential biotechnology from the 

emerging areas of structural, functional, and 

comparative genomics and proteomics, to unravel the 

complex processes of developmental biology at higher 

levels of resolution. Both the application of this 

expanding technology and the expected data from the 

Human Genome Project increase the need for support of 

infrastructure, bioinformatics, and data presentation. 

The section on Training and Education highlights the 

need for basic/clinical integrative training, as well as 

support for training in some targeted areas, such as 

clinical phenotyping, dysmorphology, teratology, genetic 

epidemiology, and informatics and data management. 

* Any research initiative supported by the NICHD involving fetal or embryonic stem cells will meet the “National Institutes of Health Guidelines for 

Research Involving Human Pluripotent Stem Cells,” which was released in August 2000. The guidelines apply to all relevant initiatives in this 

strategic planning document. 

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F R O M C E L L S T O S E L V E S 

Developmental Biology: Understanding Normal and Abnormal Development 

Scientific Goals of the Strategic Plan
 

The goal of this strategic plan is to clarify the underlying 

mechanisms of normal and abnormal developmental 

processes to provide the basis for understanding the 

formation of birth defects. In pursuit of this goal, the 

Institute will investigate birth defects from both clinical 

and basic science perspectives. Clinical studies are 

important to address the genetics, phenotyping, and 

classification of human birth defects. Basic studies that 

use experimentally manipulable systems are essential to 

clarify the underlying mechanisms of both normal and 

abnormal development. Science also has a continuing 

need to create models that test hypotheses derived from 

both scientific approaches. 

Multidisciplinary approaches mentioned in this section 

require cutting-edge technologies, such as those 

associated with structural, functional, and comparative 

genomics, proteomics, and imaging. The approaches 

addressed in the section on Research Technologies and 

Resources are expected to include (1) determining 

patterns of gene expression during development of 

specific cell types, complex tissues, and organs and 

(2) examining protein expression profiles and 

structural/functional relationships of key developmental 

proteins. 

Genetic Studies of Birth Defects 

The research in this emphasis area begins with 

describing the physical traits, or phenotype, of a patient 

and then works toward determining the genes involved 

in that defect and its underlying mechanisms with a birth 

defect. Mapping and sequencing data generated by the 

Human Genome Project will help scientists study the 

genes associated with human hereditary conditions. 

Linkage analyses of pedigrees and mapping studies are 

a mainstay of clinical genetics studies. Additional 

classification/phenotyping research and genetic 

epidemiological studies are needed to address the 

complexity of congenital anomalies, especially those 

associated with syndromes that have multiple clinical 

features. 

• Phenotype delineation. Once scientists 

phenotype or characterize the entire physical, 

biochemical, and physiological makeup of individuals 

with a specific condition, they will have a better 

understanding of the human disease process. 

Beginning in utero, the full-spectrum characterization 

will provide extremely useful information when 

compared with and correlated with the genotype of 

these individuals. Consequently, there is also a need 

to develop improved methods for phenotypic analysis, 

including syndrome delineation and natural history of 

disease. Developing registries to collect cases and 

networks to provide data on phenotype and families 

will prove vital for linkage analyses and, ultimately, for 

mapping the genes responsible for specific birth 

defects. For these reasons, the NICHD encourages 

research that links phenotyping to well-defined 

research projects; such efforts will also include clear 

and delineated plans for the eventual analysis of these 

data at the molecular level. These programs will focus 

on a tractable scientific problem and will include 

impact analyses on birth prevalence and innovative 

and novel approaches for, and technology 

development relevant to, phenotype delineation. The 

efforts will also strive to increase throughput/ 

efficiency, while making the resulting data/specimens 

widely available. In addition, the programs will 

integrate basic science activities to ensure that 

collected clinical data and specimens are productively 

channeled to the laboratory. 

• Genetic epidemiology. This comparatively new 

field of research emerged from the integration of 

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molecular genetics into traditional epidemiological 

research. Generally, genetic epidemiology focuses on 

the contribution of genetic, teratogenic, and 

environmental factors identified at the molecular level 

to the etiology, distribution, and prevention of disease 

within families and across populations. For example, 

the causes of ethnic and racial disparities in the 

incidence of certain birth defects are relevant to this 

area of research, as are collaborative and 

interdisciplinary studies of human malformations that 

integrate the latest advances in developmental and 

molecular genetics with new and innovative analyses 

of epidemiological data. Such investigations will 

provide a foundation for developing hypotheses 

concerning molecular genetics and the developmental 

biology of structural birth defects. 

Basic Mechanisms of Normal 

and Abnormal Development 

The NICHD continues to recognize research 

into the basic mechanisms of normal 

and abnormal development as 

a high priority area. 

Further, the enormous 

success and fast pace of 

advances in this field 

merit additional future 

support. This research 

focuses on using model 

systems to clarify the 

mechanistic causes of birth defects. 

Through basic research, scientists are 

beginning to identify the many factors that regulate the 

genetic networks triggering and controlling 

developmental processes. Coupled with the advances 

from the Human Genome Project, the NICHD expects 

that opportunities to foster interaction between the 

laboratory and the clinic will continue to increase. Of 

particular interest to the Institute are studies examining 

defects of gastrulation, generalized body patterning, and 

the formation of organs, such as those of the nervous, 

skeletal, and visceral systems. All of these major 

developmental events require the precise integration of 

many developmental processes, including morphogenetic 

movements, cell-cell and cell-matrix interactions, signal 

transduction, cell proliferation, and apoptosis, to name a 

few. Understanding the normal choreography of these 

developmental processes, as well as gaining insight into 

the results of genetic abnormalities or teratogenic insults, 

are essential if scientists are to make the leap from basic 

knowledge to therapeutic intervention or prevention of 

structural birth defects. Without overlooking more 

standard methodologies and physiological approaches 

to these questions, the inclusion of state-of-the-art 

genomics and proteomics technologies is inherent to 

these studies. This work will allow scientists to determine 

the patterns of gene expression during the development 

of specific cell types and complex tissues and organs, 

and to examine protein expression profiles and 

structural/functional relationships of key developmental 

proteins. Although it is likely that this work will rely 

heavily on animal models, translating the basic research 

findings to congenital structural malformations that 

are clinically significant is also 

important. Major areas of 

emphasis within basic 

mechanisms of normal and 

abnormal development 

include the following: 

• Early embryonic 

events and processes. 

The elaborate and early 

embryonic events, such as body axes 

formation, gastrulation, and neurulation, are 

crucial for normal embryogenesis and greatly 

influence both the formation of the basic body plan 

and cell fate. Because significant defects in these 

processes are frequently lethal to the embryo, 

understanding the genetic events that underlie these 

dynamic processes is critical. 

• Organogenesis. The formation of organ systems 

requires a precise integration of many developmental 

processes that involve the coordination of complex 

F R O M C E L L S T O S E L V E S 

Developmental Biology: Understanding Normal and Abnormal Development 

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FROM CELLS TO SELVES 

Developmental Biology: Understanding Normal and Abnormal Development 

genetic and developmental networks. Advances in the 

field of developmental biology now allow scientists the 

level of sophistication to study the formation of organs. 

Clarifying gene expression patterns, defining genetic 

networks, understanding matrix biology, and 

characterizing biochemical interactions are crucial for 

our understanding of structural birth defects. 

• Unique opportunities in developmental 

immunobiology and neurobiology— 

intriguing systems associated with 

“learning” and “memory.” Although this 

strategic plan focuses on anatomically evident 

structural defects, the functional ramifications of more 

subtly aberrant developmental processes also deserve 

attention. In this respect, two important areas of 

research are developmental immunobiology and 

developmental neurobiology, with each associated 

with memory and learning in slightly different 

contexts, resulting from interactions with the 

environment. The analogy is most apparent with the 

learning and memory processes of the central nervous 

system (CNS), such as when a child goes to school 

and learns to read. Similarly, in the immune system, 

the mature cells that form the body’s defenses against 

assaults from foreign antigens must “learn” and 

“memorize” the identities of invaders to protect the 

body from disease. In both the immune and nervous 

systems, even abnormalities in developmental 

processes that are not readily detected as structural 

defects have devastating functional implications, such 

as the occurrence of primary immunodeficiency 

diseases or mental retardation and learning 

disabilities. The NICHD plans to incorporate studies 

on the following topics: 

➢ Developmental immunobiology. Large gaps 

still exist in our knowledge of the developing human 

immune system. Understanding both the normal 

and abnormal development of the human fetal and 

neonatal immune system and the interactions of this 

immune system with maternal immunity has 

enormous clinical implications. Basic studies will 

provide the essential fundamental knowledge, 

understanding, and insights that researchers can 

translate into effective diagnostic procedures, safe 

and efficacious prophylactic and therapeutic 

modalities, and useful prevention strategies to 

reduce infant morbidity and mortality. Animal 

models, particularly those of mice, provide valuable 

insights into human immunobiology. Because of 

differences in the timing of T- and B-cell generation 

and the population of lymphoid organs, parallel 

studies of human and mouse immune cells at 

different developmental and functional stages are 

also important. Studies of developmental 

immunobiology will involve basic, applied, and 

clinical research on the ontogeny of immunity, the 

development of immune responsiveness, postnatal 

responses to the environment, and reproductive 

immunology. Other, more focused, research 

includes ontogeny of the normal immune system 

and host defense mechanisms, genetic programs 

governing normal and abnormal development of 

immunity and response to infection and 

immunization, and cellular and molecular 

mechanisms of immune tolerance and transfer of 

immunity during pregnancy. 

➢ Developmental neurobiology. Like all 

developing systems, the CNS is shaped by the 

developmental and genetic programs of the 

organism, as well as by numerous geneenvironmental interactions. In its initial phases, the 

developing CNS has many processes in common 

with the formation of other organ systems. 

However, minor flaws in subsequent, complex 

processes, such as those associated with synapse 

formation and higher levels of integration, can result 

in subtle structural defects that have devastating 

functional implications. Consequently, in addition to 

supporting basic research in classical areas such as 

axonal guidance, tissue differentiation, and gene 

discovery in the developing CNS, the NICHD will 

also place an emphasis on studies that develop 

criteria for and collect descriptive data on various 

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F R O M C E L L S T O S E L V E S 

Developmental Biology: Understanding Normal and Abnormal Development 

neurological syndromes. These endeavors represent 

a prime example of the need for a merger of 

detailed phenotyping and gene expression 

analyses. The proactive development and inclusion 

of these data in comprehensive databases for 

neurological disorders will prove invaluable for 

analyses of both structural defects and abnormal 

brain function, which would benefit behavioral 

scientists searching for a genetic cause for a specific 

syndrome or functional deficit. The NICHD will 

coordinate efforts to support research and database 

development, both between its own branches 

involved with different aspects of neurobiology 

research and with other Institutes, research 

institutions, and organizations from the private 

sector with shared interests in developmental 

neurobiology. 

Development of Model Systems 

The discovery of the highly conserved nature of 

developmental processes across species, from worms 

(C. elegans), flies (Drosophila), zebrafish (D. rerio), frogs 

(Xenopus), and mice to humans, has been an important 

conceptual advance. For many years, scientists have 

used animal models to clarify and understand 

developmental processes and identify many genes 

involved in human development. The next 

step in this development is to create 

or identify models for testing 

hypotheses that are generated 

as a result of clinical and 

basic studies. Recently, 

scientists also established the 

significance and potential 

applications of embryonic stem 

cells. Thus, both animal and stem 

cell models are essential components of 

research in this emphasis area. 

• Animal models. Multidisciplinary studies using 

appropriate animal model systems are essential to 

clarify the molecular, biochemical, and morphological 

aspects of crucial, basic processes such as cell 

proliferation, cell differentiation, and cell interactions, 

as well as the complex processes of gastrulation, 

patterning, neurulation, and organogenesis. Such 

investigations will improve scientific insight into 

mechanisms of development, facilitate the identification 

of critical developmental periods, and enable 

researchers to verify the genetic and environmental 

miscues that give rise to conditions like neural tube and 

skeletal defects. The conservation of genes, genetic 

networks, and developmental pathways across the 

animal kingdom provides credence for using diverse 

models, such as C. elegans, Drosophila, Xenopus, the 

zebrafish, and mice to study human developmental 

processes. Consequently, the knowledge provided by 

work on model systems will also provide the basis for 

translational studies of human congenital defects. This 

knowledge will lead to the improvement of early 

diagnostic procedures and the development of gene 

therapies that can ameliorate or prevent birth defects. 

The NICHD cannot overemphasize the importance of 

continued support for the use of animal models to study 

development. To accomplish its goal, the Institute will 

support the use of all animal models, including 

natural mutants, targeted/induced 

mutants, and transgenic animals, 

and the development of new 

methods to target gene 

expression (e.g., selective 

spatial or temporal 

expression and genetically 

controlled cell ablation to study 

the function of specific cell 

populations) in model systems. These 

efforts will also incorporate a critically needed 

mechanism by which information about animal models 

can be quickly disseminated and advertised to the 

research community. 

Curly tail mouse photo provided by Stanton K. Short, The Jackson 

Laboratory, Bar Harbor, Maine 

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FROM CELLS TO SELVES 

Developmental Biology: Understanding Normal and Abnormal Development 

• Embryonic stem cells. 	Embryonic and other 

stem cells of differentiated tissues provide important 

models for understanding basic processes 

associated with development and 

differentiation. Although research 

on embryonic stem cell biology 

using animal models is still in its 

early stages, it is a very 

promising approach to 

unraveling developmental 

processes. Once the processes 

and factors that govern 

proliferation and differentiation of 

embryonic stem cells are better 

understood, this approach offers the potential for 

therapeutic interventions in birth defects and 

abnormal immunological development, particularly 

those involving cell and tissue replacement. 

To accomplish this goal, the Institute 

will support studies to characterize 

and define embryonic and 

postnatally derived stem cells 

from different species, identify 

factors that stimulate and trigger 

the proliferation and 

differentiation of stem cells 

toward various cell lineages, and 

foster the use of stem cells as a tool 

for studying the processes of differentiation 

and cell lineage determination. 

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F R O M C E L L S T O S E L V E S 

Research Technologies and Resources
 

For innovative and creative scientific projects to 

succeed, the appropriate infrastructure, resources, 

and technologies must be available. Some of the 

technologies and resources listed below overlap because 

their integration is necessary to achieve a scientific end; 

for instance, imaging, genomics, and computational/ 

bioinformatics are all involved in developing 

atlases/gene expression databases. Cost is a major 

consideration in these endeavors. Establishing 

databases or genomic/proteomic resources is costly 

enough; however, maintaining them in perpetuity is 

extremely expensive. Consequently, while the NICHD 

understands the importance of developing human and 

animal databases and resources and remains committed 

to the task, maintaining these databases requires the 

coordinated support of several Institutes, particularly 

those that are more technology-driven, in addition to 

private organizations with similar goals. 

Functional Genomics and 

Proteomics 

Genomics and proteomics represent important scientific 

strategies for capitalizing on genome sequencing to 

address questions raised in the developmental biology 

and birth defects emphasis areas. The research areas of 

functional genomics and proteomics deal with the 

analysis of gene activity and the processes that lead to 

the expression of proteins, as well as the integrated, 

systematic view of protein interactions and their 

relationships to cell function. The combination of these 

powerful approaches provides a means of analyzing 

regulation at many levels. These strategies are also 

extremely important when used in conjunction with 

imaging technologies to catalog gene expression in 

databases and atlases. Indeed, the use of these new 

methodologies is embedded in the very fiber of the 

studies recommended in the section on Scientific Goals 

of the Strategic Plan. At the same time, as new fields, 

functional genomics and proteomics have provided 

immense amounts of data and will continue to do so well 

into the future. Because researchers anticipate that onehalf to three-fourths of all human genes will prove 

important in developmental processes, generating 

efficient and uniform data, cataloging the data, and 

presenting them in a form that is useful to scientists pose 

complex challenges to genomic and proteomic research 

strategies. Possible solutions to these challenges include 

the following: 

• Promoting the use of computational biology and 

bioinformatics to address issues of normal and 

abnormal development. 

• Developing new strategies to support mutagenesis and 

phenotyping to identify and characterize genes 

involved in normal and abnormal development. 

• Identifying new methods of spatial/temporal 

inactivation of genes in specific cell types in model 

systems. 

• Developing new techniques for using proteomics to 

study normal and abnormal development. 

• Developing techniques to isolate specific cell types 

from tissues to accurately and systematically assess 

cell-type gene expression. 

Imaging Technology and 

Visualization of Development 

Processes 

Developing these technologies has implications both for 

basic and clinical research. Advanced imaging 

technologies allow researchers to develop models 

showing morphogenetic movements in the temporal 

development of organ systems and to capture gene 

Developmental Biology: Understanding Normal and Abnormal Development 

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Developmental Biology: Understanding Normal and Abnormal Development 

expression data for inclusion in a database. Emerging variety of public and private organizations. Major areas 

technologies will enable scientists to visualize of interest include the following: 

developmental processes and to monitor cellular and 

molecular changes at a level of resolution previously not 

possible. In addition, advanced imaging techniques can 

be used for diagnosing abnormal development in utero. 

The NICHD recognizes that support for the following 

areas is essential for the future of integrated research in 

basic and clinical developmental biology: 

• Promoting the development of noninvasive imaging 

methodologies to study developmental events in 

animal models. 

• Translating high-resolution technology, currently used 

for analyzing developmental defects in animal models, 

to humans for prenatal and postnatal assessment. 

• Developing more sophisticated techniques for threedimensional rendering to allow for “fly through” 

analysis of fetal structures. 

• Developing safe contrast agents or molecular probes 

to enhance imaging of prenatal and postnatal subjects 

to assess anatomic or genetic abnormalities. 

Developmental Databases 

Although a number of high-quality developmental 

databases currently exist, information regarding what is 

available requires better dissemination. In addition, 

although the creation of new databases will increase 

resources, the content of these databases needs careful 

consideration and focus to provide the maximum benefit 

and cost-effectiveness. Both new and existing registries 

need to adopt a uniform collection process so that data 

are comparable. The NICHD is interested in developing 

such an infrastructure and intends to collaborate with 

parties who have successfully developed such databases 

and registries. Creating a database to which 

researchers could submit their mutants before publishing 

their research findings could foster and expedite 

contributions to that database by other investigators. 

Maintaining such databases could be shared among a 

• Establishing and maintaining databases of 

developmental mutations in vertebrate animal models. 

This effort would entail fostering registries of widely 

useful mutants, such as “effector” mice for work with 

knockout mutants, mice with conditional or timespecific knockouts, or those with genetically controlled 

cell ablation, to study function of a particular cell 

population. 

• Developing high-quality developmental atlases of 

commonly used vertebrate models using a variety of 

imaging techniques and making the atlases broadly 

accessible to the community (i.e., electronically). 

• Establishing and maintaining morphological databases 

of patterns of developmental gene expression. 

• Creating similar atlases and databases related to other 

aspects of human development. 

• Establishing and maintaining gene expression 

databases and digital atlases of development and 

ensuring that resources from developmental human 

and model systems are linked to facilitate comparisons 

between species. 

Programs for the Study of the 

Developmental Biology of Birth 

Defects 

An overriding and important issue in studying birth 

defects is understanding the normal developmental 

processes and determining how these processes are 

perturbed to cause birth defects. As mentioned, much of 

what we know about development has come from using 

animal models. The Institute must take advantage of the 

knowledge that results from animal models and apply 

this to human congenital abnormalities by supporting 

multidisciplinary birth defects research programs or 

networks that bring together basic and clinical 

researchers to enhance translation of basic findings to 

clinical applications. 

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Developmental Biology: Understanding Normal and Abnormal Development 

Training and Education
 

As scientific and technological advances continue at a 

rapid rate, the increasing sophistication of 

methodologies will require scientists to specialize their 

knowledge in these new approaches, which will heighten 

the need for multidisciplinary collaborations to address 

research issues. Scientists must also be conversant in 

new methodologies and approaches used by their 

collaborators to strengthen these interactions into 

becoming productive, successful, and enduring 

collaborations. In addition, while there is an increasing 

need for a diverse and well-trained work force for birth 

defects research, that need extends beyond trained 

laboratory investigators. The NICHD will expand the 

small clinical and epidemiological work force studying 

birth defects to ensure the availability of valuable 

collaborators for basic scientists interested in studying 

human birth defects. The Institute emphasizes the 

following areas: 

• Encouraging interdisciplinary training of biomedical 

researchers and computational/bioinformatics 

biologists. 

• Promoting training of and interaction between basic, 

epidemiological, and clinical investigators. 

• Fostering targeted training support for areas in critical 

need, such as phenotyping human birth defects, 

comparative phenotyping in animal models down to 

the level of the cell, genetic epidemiology, and 

bioinformatics. 

• Developing support mechanisms that will promote 

interdisciplinary training opportunities for young 

investigators. 

• Supporting programs to train clinical investigators in 

birth defects and developmental biology research. 

• Encouraging efforts to help senior investigators move 

into new research areas with new model systems. 

• Promoting training for investigators in more than one 

model system. 

• Examining the potential for providing high school and 

undergraduate students with training in needed areas, 

particularly bioinformatics. 

• Creating a graduate student technical program. 

• Fostering reliable outsourcing of now routine tasks, 

such as cloning, making transgenic mice, and some 

chip-based technologies, as laboratories become 

burdened with these tasks. However, since these 

techniques must also be readily available for training 

purposes, the Institute will consider providing for 

additional core facilities at other research institutions. 

For example, http://www.geneclinics.com and 

http://www.genetests.org, currently funded by the 

National Institutes of Health, provide Web pages that 

list laboratory tests for various genetic diseases as well 

as investigators who will perform these services. 

These sites could serve as models for other 

developmental biology sites. Again, given the cost of 

maintaining such a site, the NICHD will need to make 

its choice of areas carefully. 

12
 
F R O M C E L L S T O S E L V E S 

Developmental Biology: Understanding Normal and Abnormal Development 

Appendix—Roster of Advisors 

Although this document has benefited from the input of many scientists within and outside the NICHD, and from the 

general public, we wish to particularly note the advice of the following members of the strategic plan working group: 

R. Rodney Howell, M.D., Co-Chair 

University of Miami School of Medicine 

David L. Rimoin, M.D., Ph.D., Co-Chair
 

Cedars Sinai Medical Center
 

Leslie G. Biesecker, M.D.
 

National Human Genome Research Institute
 

National Institutes of Health
 

Elwood Linney, Ph.D.
 

Duke University Medical School
 

Gail Martin, Ph.D.
 

University of California, San Francisco
 

Donald Mattison, M.D. 

March of Dimes 

Maximilian Muenke, M.D. 

National Human Genome Research Institute 

National Institutes of Health 

E. Albert Reece, M.D.
 

Temple University School of Medicine
 

Urs Rutishauser, Ph.D.
 

Memorial Sloan-Kettering Cancer Center
 

Christopher B. Wilson, M.D.
 

University of Washington
 

13
 
For additional copies of this strategic plan, or for more information on contacts or related issues, 

please contact the NICHD Clearinghouse at 

P.O. Box 3006
 

Rockville, MD 20847
 

Phone: (800) 370-2943
 

Fax: (301) 496-7101
 

Web: http://www.nichd.nih.gov/publications/
 

For additional information about other NICHD strategic plans and research, please visit our Web site at 

http://www.nichd.nih.gov/ 
U.S. Department of Health and Human Services

Public Health Service

National Institutes of Health

Eunice Kennedy Shriver National Institute 

of Child Health and Human Development

http://www.nichd.nih.gov/

February 2001