Address: Morgridge Institute for Research, 3266
Telephone: (608) 316-4105
Germ cell development and regeneration in planarians; developmental biology of parasitic flatworms
Developmental biology; parasitology; genomics
Research in the Newmark laboratory utilizes the tools of molecular cell biology and functional genomics to address several major biological problems for which planarians serve as excellent models.
Differentiation of the Regenerative Stem Cells: Roles in Regeneration and Tissue Maintenance
Planarians can regenerate a complete animal from a tiny fragment of tissue; this amazing regenerative ability is based upon a population of somatic stem cells maintained in the adult. How are these stem cells specified to adopt specific fates? How is their differentiation choreographed to correctly replace the missing structures? How are newly differentiated cells integrated into functional tissues and organs, during regenerative and homeostatic processes? How are stem cell proliferation and differentiation regulated systemically? We address these and related questions using the planarian, Schmidtea mediterranea, as a model, combining high-throughput in situ hybridization screens to identify cell type-specific markers, with transcriptomic analyses and functional studies using double-stranded RNA-mediated genetic interference (RNAi).
Regulation of Germ Cell Development and Differentiation
We are also interested in understanding the mechanisms by which germ cells are specified, and how physiological/environmental signals regulate their proper differentiation. In contrast to the commonly studied genetic model invertebrates, in which localized determinants specify germ cells in the early embryo, planarians use inductive signals to form their germ cells from the somatic stem cells much later in development. Thus, the functional genomic resources available for studying planarians can be used to examine inductive germ cell specification and the factors required to convert a somatic stem cell into a germ cell. We are currently using unbiased, genome-wide approaches to identify both intrinsic and extrinsic factors required for proper germ cell development.
Using planarians as models for understanding parasitic flatworms
Schistosomes are parasitic flatworms and are the causative agents of schistosomiasis, a major neglected tropical disease affecting hundreds of millions of people. Although parasitic flatworms display several striking differences in their life cycles relative to their free-living relatives, they also share many common features. We are capitalizing on the experimental accessibility of planarians to help us understand several fundamental aspects of schistosome biology.
Roberts-Galbraith, R.H., Brubacher, J.L., and P.A. Newmark. 2016. A functional genomics screen in planarians reveals regulators of whole-brain regeneration. eLife 5: e17002.
Saberi, A., Jamal, A., Beets, I., Schoofs, L., and P.A. Newmark. 2016. GPCRs direct germline development and somatic gonad function in planarians. PLOS Biology 14: e1002457 (cover).
Collins III, J.J., Wendt, G.R., Iyer. H., and P.A. Newmark. 2016. Stem cell progeny contribute to the schistosome host-parasite interface. eLife 5: e12473.
Rozario, T. and P. A. Newmark. 2015. A confocal microscopy-based atlas of tissue architecture in the tapeworm, Hymenolepis diminuta. Experimental Parasitology 158: 31-41.
Roberts-Galbraith, R.H. and P. A. Newmark. 2015. On the organ trail: insights into organ regeneration in the planarian. Curr. Opin. Gen. Dev. 32: 37-46.
Wang, B., Collins III, J.J., and P. A. Newmark. 2013. Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni. eLife 2:e00768.
Sikes, J.M. and P. A. Newmark. 2013. Restoration of regeneration in a planarian with limited regenerative ability. Nature 500: 77-80.
Chong, T., Collins III, J.J., Brubacher, J.L., Zarkower, D., and P. A. Newmark. 2013. A sex-specific transcription factor controls male identity in a simultaneous hermaphrodite. Nature Communications 4: 1814.
Collins III, J.J., Wang, B., Lambrus, B.G., Tharp, M., Iyer, H., and P. A. Newmark. 2013. Adult somatic stem cells in the human parasite, Schistosoma mansoni. Nature 494: 476-479.
Roberts-Galbraith, R.H. and P. A. Newmark. 2013. Follistatin antagonizes Activin signaling and acts with Notum to direct planarian head regeneration. Proc. Natl. Acad. Sci. USA 110: 1363-1368.