Our laboratory studies genes important for embryonic development in mice, and the relation between mutations in these genes and both congenital and acquired human disease. Our analyses focus on the Notch pathway, an evolutionarily conserved cell communication and signaling system, and on genes of the Snail superfamily, which encode transcriptional repressor proteins.
We have created and analyzed numerous genetically engineered mouse models to understand the essential functions of individual components of these pathways. We have also generated mouse models for inherited human disease syndromes such as Alagille syndrome, and for common birth defects such as cleft palate, craniosynostosis, and congenital heart defects, such as outflow tract patterning defects and patent ductus arteriosus. Current areas of interest include the role of Notch signaling in cardiovascular development, and in skeletal muscle and mesenchymal stem cells.
Figure 1. Defects in embryonic development in Notch pathway mutant mice. In all panels, the control embryo is on the left, with the mutant on the right. A) Patent ductus arteriosus in Jag1 conditional mutant embryos. B) Rib and vertebral defects in Notch-regulated ankyrin repeat (Nrarp) mutant embryos. C) Defects in formation of sensory cells of the inner ear in Jag1 conditional mutant embryos. D) Kidney defects in Notch2 hypomorphic mutant embryos.
Scientific Manager I
Research Interests: Mouse embryonic development
Pardo-Saganta A, Tata PR, Law BM, Saez B, Chow RD, Prabhu M, Gridley T, Rajagopal J (2015) Parent stem cells can serve as niches for their daughter cells. Nature 523:597-601.
Gridley T, Kajimura S (2014) Lightening up a notch: Notch regulation of energy metabolism. Nature Med 20: 811-812.
Gridley T., Groves AK (2014) Overview of genetic tools and techniques to study Notch signaling in mice. Meth Molec Biol 1187:47-61.
Xu J, Gridley T (2013) Notch2 is required in somatic cells for ovarian germ cell nest breakdown and primordial follicle formation. BMC Biol 11:13.
Chen Y, Gridley T (2013) Compensatory regulation of the Snai1 and Snai2 genes during chondrogenesis. J Bone Min Res 28:1412-1421.
Bradley CK, Norton CR, Chen Y, Han X, Booth CJ, Yoon JK, Krebs LT, Gridley T (2013) The Snail family gene Snai3 is not essential for embryogenesis in mice. PLoS ONE 8:e65344.
Battle R , Alba-Castellón L, Loubat-Casanovas J, Armenteros E, Franci C, Stanisavljevic J, Banderas R, Martin-Caballero J, Bonilla F, Baulida J, Casal JI, Gridley T, García de Herreros A (2013) Snail1 controls TGF-β responsiveness and differentiation of Mesenchymal Stem Cells. Oncogene 32:3381-3389.
Krebs LT, Bradley CK, Norton CR, Xu J, Oram KF, Starling C, Deftos ML, Bevan MJ, Gridley T (2012) The Notch-regulated ankyrin repeat protein is required for anterior-posterior somite patterning. Genesis 50:366-374.
Tao G, Levay AK, Gridley T, Lincoln J (2011) Mmp15 is a direct target of Snai1 during endothelial to mesenchymal transformation and endocardial cushion development. Dev Biol 359:209-221.
Feng X, Krebs LT, Gridley T (2010) Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion. Development 137:4191-4199.
- Professor, Department of Medicine, Tufts University School of Medicine, Boston, MA
- Professor, Tufts Clinical and Translational Science Institute, Tufts University School of Medicine, Boston, MA
- Faculty Member, Molecular, Cell, and Developmental Biology Graduate Program, Tufts University Sackler School of Graduate Biomedical Sciences, Boston, MA
- Member, Graduate Faculty, Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME
- Adjunct Faculty, The Jackson Laboratory, Bar Harbor, ME
- Editorial Board, Genesis
- External Advisory Board, Jackson Laboratory Gene Expression Database
- Reviewer, Genetics of Health and Disease Study Section, National Institutes of Health (2012)
- Reviewer, Development 2 Study Section, National Institutes of Health (2012, 2013)
- Member, American Heart Association
- Vice Chair, Maine Medical Center Institutional Review Board
- Lecturer, Cell Biology of Tissue Development and Function, Graduate School of Biomedical Sciences, University of Maine, Orono
- Lecturer (2015), Advanced Mouse Modeling: Relevance to Human Disease, Graduate School of Biomedical Sciences, University of Maine, Orono