Spermatogonial stem cells from testes of adult mice and germline stem cells from testes of neonatal mice can generate pluripotent cells with developmental potential similar to embryonic stem (ES) cells. These results suggest that germ cells from the testes could be used to provide stem cells for tissue engineering and regenerative medicine. Hypotheses that ES cells may be derived from germ cells provide a similar impetus for understanding the mechanisms that specify and maintain the germ cell lineage. Current understanding of germ cell specification mechanisms is based largely upon studies of model organisms that utilize cytoplasmic determinants to specify their germ cells (e.g., Drosophila and C. elegans). In contrast, many organisms (including mammals) utilize inductive signals to specify germ cell fate. Studies of inductive specification have been limited almost exclusively to mouse and many questions remain unanswered. For example, are there conserved inductive signals that specify germ cell fate? What are the mechanisms that activate germ cell-specific patterns of gene expression? The freshwater planarian, Schmidtea mediterranea, serves as a useful model for studying these questions. It has prodigious regenerative abilities, based upon a population of stem cells, that allow it to regenerate a complete animal from a tiny body fragment;the germ cell lineage can also be regenerated. This work will capitalize on the functional genomic tools available for studying S. mediterranea to dissect the mechanisms by which inductive signals specify germ cell fate. Microarray analyses will be performed to identify genes that are expressed differentially between animals that have early germ cells and animals that lack them. Next generation sequencing technologies will be utilized to characterize gene expression changes during the initial course of germ cell development. High through put in situ hybridization will be used to validate candidate genes identified by these analyses. The functions of these differentially expressed genes will then be examined by RNA interference. These studies have the potential to identify conserved genes that are required for proper germ cell development.

Public Health Relevance

Germ cells give rise to the next generation by producing gametes (eggs and sperm). Because germ cells are capable of generating all cells in an organism, it is important for us to understand how these cells are produced and regulated. This research uses a simple animal, the planarian, to understand how germ cells develop. It is relatively easy to identify genes and study their functions in planarians;analyzing genes shared between planarians and mammals will help us decipher how these genes function in mammalian germ cells.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD043403-06A1
Application #
7524691
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Coulombe, James N
Project Start
2003-01-09
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
6
Fiscal Year
2009
Total Cost
$272,909
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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Saberi, Amir; Jamal, Ayana; Beets, Isabel et al. (2016) GPCRs Direct Germline Development and Somatic Gonad Function in Planarians. PLoS Biol 14:e1002457
Ong, Ta-Hsuan; Romanova, Elena V; Roberts-Galbraith, Rachel H et al. (2016) Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea. J Biol Chem 291:8109-20
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Iyer, Harini; Collins 3rd, James J; Newmark, Phillip A (2016) NF-YB Regulates Spermatogonial Stem Cell Self-Renewal and Proliferation in the Planarian Schmidtea mediterranea. PLoS Genet 12:e1006109
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Tharp, Marla E; Collins 3rd, James J; Newmark, Phillip A (2014) A lophotrochozoan-specific nuclear hormone receptor is required for reproductive system development in the planarian. Dev Biol 396:150-7
Rouhana, Labib; Weiss, Jennifer A; King, Ryan S et al. (2014) PIWI homologs mediate histone H4 mRNA localization to planarian chromatoid bodies. Development 141:2592-601
Brubacher, John L; Vieira, Ana P; Newmark, Phillip A (2014) Preparation of the planarian Schmidtea mediterranea for high-resolution histology and transmission electron microscopy. Nat Protoc 9:661-73
Rouhana, Labib; Weiss, Jennifer A; Forsthoefel, David J et al. (2013) RNA interference by feeding in vitro-synthesized double-stranded RNA to planarians: methodology and dynamics. Dev Dyn 242:718-30

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