Grants and Contracts per year
Grants and Contracts Details
Introduction We are developing genome resources to better enable salamanders as models for human health and disease research. Much of our work is focused on nIRNA transcript discovery using the Mexican axoloti, Ambystoma mexicanum and the Eastern Tiger Salamander, A. tigrinum tigrinuen. Sequence information from these transcripts allowed us to develop a custom Affymetrix GeneChip to gain gene expression insights of two unique developmental processes: tissue regeneration and metamorphosis (Monaghan et al., 2007; Page et al., 2007, 2008). Results of a more recent microarray analysis of metamorphosis yielded a novel and exciting discovery that we believe can be expanded upon with supplemental funding to establish a new amphibian model for human disease. We discovered dramatic differences in gene expression between the developing brains of salamanders that undergo metamorphosis versus salamanders that fail to undergo metamorphosis (paedomorphosis). Because mechanisms of brain development and function are conserved among vertebrates, these alternate, developmental outcomes - metamorphosis vs paedomorphosis - provide a model to identify molecular mechanisms that alter the trajectory of human brain development. In particular, metamorphosis and paedomorphosis in salamanders depend upon maturation of the same neuroendocrine regulatory mechanisms that are implicated in complex mental and physical health disorders, including depression, schizophrenia, autism, and Parkinson's disease. Also, because paedomorphic salamanders retain many juvenile traits throughout life, this model can provide novel insights about the aging process and how it affects neurogenesis and neural plasticity. Background Genetic and environmental factors can alter the normal trajectory of brain development during embryonic, natal, and post-natal phases of life, and these alterations can have lasting effects on molecular function and physiology, and mental health. That these observations holds true for all vertebrates suggests that non-mammalian species can provide novel insights about human brain function. Supplemental funding is requested to develop a new amphibian model in which alternate and adaptive modes of brain development, which are determined by allelic variation at a single locus, yield distinct adult phenotypes. The model is novel relative to other vertebrates because it provides a lengthy and accessible window of time to investigate the molecular and environmental basis of adult phenotypic variation arising from alternate trajectories of brain development. The proposal has three sections. First, the literature is briefly and incompletely reviewed concerning the role of the hypothalamus-pituitary-adrenal (HPA) axis in mediating stress and directing development in mammals and salamanders. The 2nd section introduces the new salamander genetic model that we propose to develop. In the 3"~ section, rationales are provided for funding to further develop our model. This project complements ongoing efforts to develop genomic resources for the salamander model system. The resources provided by this supplement will justif~' applications to further develop this model under PA-06-445: Development of Frontal Cortex and IAmbic System and Their Roles in Drug Abuse or Mental Health.
|Effective start/end date||9/23/08 → 3/31/11|
- National Center for Research Resources
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- 1 Finished
Genome Resources for Model Amphibians
National Center for Research Resources
10/1/01 → 7/22/12
Project: Research project