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Development White Paper (PDF - 128KB)

Created on March 31, 2011

6 Submitted Comments on Development

Excellent document. Very comprehensive, and insightful. The question I had: most plasticity discussion focused on the developing brain. not knowing an answer, I am wondering: what is the relationship between plasticity and injury/repair? Specifically as they relate to preterm infants who survive neonatal disorders with residual organ damage? The most well known chronic condition is BPD. But, less well understood are other large systemic organs--the kidney, the heart, the GI system, and of course the lungs. Consider an adult born at very preterm gestation: will she have permanently smaller kidneys? What about her heart? will she increase her myocytes in number postnatally, or simply develop hypertrophy of the myocytes to accomodate function? What are the processes interacting organ repair after injury (oxygen plus prematurity-induced lung injury) and repair that leads to fibrosis of airways? I am not sure exactly where this fits in this document; but I think some consideration should be given to such questions as noted above. Sincerely, Tonse

Submitted by Tonse Raju on March 31, 2011 at 2:05 PM

The document has many strengths, but in the opinion of several P.I.s in the Program of Cellular Regulation and Metabolism in the Intramural Research Program, it fails to acknowledge the importance of biochemical analysis of cellular and developmental mechanisms, and the central role played by non-vertebrate model systems in this kind of research. Understanding development requires a sophisticated mechanistic understanding of cell function and regulation, and cell-cell interactions. The unusually strong emphasis on systems biology in the White Paper seems to assume that all of the pathways and macromolecular assemblies in the cell are essentially understood, and we need only to figure out how they?re integrated into multicellular systems. This is not the case, of course, and there will be a continued strong need for in-depth biochemical and structural analysis of cellular and developmental pathways to provide high quality mechanistic data for computational biologists to work with. It should be noted that the word ?biochemistry? does not appear once in this document. A related omission is the failure to acknowledge the importance of non-vertebrate model systems, including bacteria, yeast, Drosophila, and nematodes, where the most powerful genetic tools can be coupled with biochemistry, biophysics, structural biology and imaging to rapidly dissect cellular and developmental pathways. Our understanding of the mechanism of the cell cycle, transcriptional control, early embryonic patterning, and RNA silencing and microRNAs, just to name a few topics, owes much to the pioneering work done with these systems. In fact, they?ve led the way in systems biology and continue to push the envelope in genome-wide analysis of genetic and protein interactions and metabolomics. These model systems will continue to be invaluable for rapidly dissecting the functions of genes impaired in developmental defects or diseases. In our view, a vision statement for the next decade of research on developmental biology supported by our institute should include the critical importance of research aimed at dissecting the molecular machines and pathways with critical roles in cellular function and development at the biochemical and molecular levels, taking advantage of all model systems, including the non-vertebrate models that achieve the most powerful combination of genetics and biochemistry.

Submitted by Alan Hinnebusch on April 18, 2011 at 11:15 AM

Much of what is recommended in the NICHD white paper on Development are improvements to our ability to identify genes with important developmental roles or to expand our capacity to dissect molecular pathways and describe critical cellular and molecular-level functions involved in development. These are valid and important recommendations that should be pursued. However these goals are conservative rather than visionary in the sense that they are in essence logical extensions of present ongoing efforts. Over the past several decades the approaches used by developmental biologists have resulted in a wealth of detailed molecular-level descriptions for developmental phenomena. However this information has only provided isolated insights of mechanistic understanding. If anything, the successes of these hypothesis-driven and reductionist approaches have taught us that development is exceptionally complex and that intuitive models of developmental processes are of limited utility beyond describing simple linear pathways. Ultimately, a fundamental understanding of development requires the assimilation of many levels of genomic, biochemical, and biophysical information into models that are quantitative, predictive, and experimentally verifiable. In this context, the white paper understates the importance of systems biology to the future of developmental biology. In particular, it is notable that there is no specific mention of regulatory network analysis for developmental processes. This is a bottom-up approach that is a key area of developmental systems biology. This approach to developmental biology has been pioneered by Eric Davidson and his colleagues in assembling a gene regulatory network model of early sea urchin embryogenesis. Recent technological advances in genomic sequencing, rapid analysis of gene regulatory elements, and quantitative multiplex assays of gene expression now make it feasible to expand this approach to other model organisms, including vertebrates. It is important to recognize and foster this approach since the construction of network models for regulatory processes offers the potential to link isolated molecular and mechanistic descriptions of developmental processes into a foundational framework allowing important causal relationships to be identified and predictively understood.

Submitted by James Coulombe on April 20, 2011 at 11:56 AM

How will these visions be implemented in an environment of severs budget cuts?

Submitted by Anonymous Guest on May 29, 2011 at 11:50 AM

The Endocrine Society appreciates the opportunity to provide feedback on the white papers developed from the Vision Workshops held by the NICHD. A significant portion of the Society's basic researchers apply for funding through NICHD, and given the tremendous overlap between Society members' research interests and those of the NICHD, The Endocrine Society considers the Institute's scientific visioning process to be an important milestone for the continued advancement of endocrine science.

The Society supports the mission presented in the Development white paper but is concerned that the paper lacks clearly defined plans of action. The community resources section outlines needs for the next ten years and includes suggestions for actions such as the creation of banks of tissue and DNA from children with malformations. However, other sections do not make it clear how priorities will be established. The inclusion of more directed plans would be a welcome addition in outlining potential funding opportunities in the next ten years. Several examples of areas of opportunity that could be expanded are described below.

The authors state that "Research is needed in experimental and clinical situations to explore and comprehend the entire exposome (environmental exposures), including nutrition, during embryonic development." This could be expanded to include objectives such as: determine the environmental exposures that affect fetal development, utilize populations with isolated exposures to determine effects on development, determine the effect of excess carbohydrate and caloric intake on fetal development, and catalog the effects of known environmental exposures on fetal development in model systems and humans.

The white paper identifies the objective to "integrate information from diverse organisms, including humans, to enhance our knowledge of conserved aspects of basic developmental processes." This could be further expanded to include an objective to create a cross-species database to compare genes, mutations, and pathways throughout development in mouse and human, and/or to generate cross-species, comparative, and comprehensive bioinformatics systems to examine developmental genetics, pathways, and environmental factors. This could include an objective for the establishment of a comprehensive platform to integrate basic developmental processes across species; including genetic and mutation information as well as knockout and knockdown models.

Submitted by Kelly Mayo on June 1, 2011 at 11:29 AM

There is increasing evidence that early life influences may contribute to bone health later in adulthood. There is not mention of muscle bone development in this white paper and how it may influence not only child health, but long-term health.

Submitted by Bonny Specker on June 2, 2011 at 10:45 AM

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Last Reviewed: 06/04/2012