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Jaime Rivera, Ph.D.
Academic Role: Assistant Professor
Faculty Appointment(s) In:
Cell Biology
Morphogenetic and Molecular Analysis of Mammalian Development
Our research is centered in understanding the morphogenetic processes and the molecules that guide the development of the mammalian embryo from pre-implantation stages to the initial stages of organogenesis using the mouse as a model system. Our rationale is that understanding the basic mechanisms that guide cells and tissues during early embryogenesis is relevant not only in understanding normal development or what goes wrong during abnormal development but also in the advancement of research fields that include cancer and stem cells.
We employ a variety of embryological, cellular, molecular and genetic approaches. These include lineage analysis, chimeras and embryo culture as well as time-lapse imaging, tissue specific knockouts, wholemount in situ hybridization and immunofluorescence. We also utilize embryonic stem cells for gene targeting.
We have previously shown that the mouse conceptus at early post-implantation stages is a dynamic and molecularly patterned structure. Our studies demonstrated that the extra-embryonic component of the developing conceptus, particularly the visceral endoderm, undergoes dramatic cell movements and is composed of morphological and molecularly distinct cell populations. These studies provide evidence that interactions between embryonic and extra-embryonic tissues play a crucial role in shaping the mouse embryo. We are defining the role that these embryonic/extra-embryonic interactions play in patterning the embryo.
One focus of our laboratory is to understand how and when the primary body axes of the embryo -the anteroposterior, dorsoventral and mediolateral axes- are established during embryogenesis. Currently, we are determining the role of Wnt3 in the development of the primitive streak and establishment of the anteroposterior axis.
A hallmark of our research is the use of clonal analysis in cell fate determination. Clonal analysis permits assessment of the position and nature of the descendants of a single labeled cell. These studies are fundamental for understanding how pluripotent cells choose a particular fate as the embryo progresses in development. We are using this technique to determine the spatial relationships between cells that signal the development of organs as diverse as the brain, heart, placenta and endodermal derivatives such as the liver and pancreas.
The importance of the early stages of embryogenesis for proper embryo development is underscored by the fact that thirty percent of human pregnancies are lost at early post-implantation stages. We strongly advocate fundamental research in early embryogenesis and are confident that our basic understanding of how the embryo develops will translate to clinical applications.
Figures
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| Figure 1. Expression of Wnt3 in embryos between 5.5 and 6.5 days of gestation. The expression of Wnt3 in the posterior visceral endoderm and subsequently posterior epiblast marks the location and polarity of the anteroposterior axis as early as 5.5 dpc. |
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| Figure 2. Clonal analysis of the trophoblast component of the blastocyst. A polar trophectoderm cell from a blastocyst derived from the ROSA26-LacZ reporter line, was injected with an expression vector coding for Cre recombinase and Rhodamine dextran (B). The labeled embryo was transferred into a pseudopregnant female and dissected at 6.5 dpc. ß-galactosidase positive descendants (blue), indicating Cre/lox recombination, are visible in the ectoplancental cone region of the embryo (C). |
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Figure 3. Molecular differences in the visceral endoderm layer of the conceptus. Egg cylinder stage embryo dissected at 5.75 days post-coitum. The promoter of Hhex, a homeobox containing gene, drives expression of green fluorescent protein in the anterior visceral endoderm (AVE). Red fluorescence marks cell-cell boundaries revealed by an anti-E-Cadherin antibody. The nuclei shown in blue are stained with DAPI.
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Publications
Cowley DO, Rivera-Pérez JA, Schliekelman M, He YJ, Oliver TG, Lu L, O'Quinn R, Salmon ED, Magnuson T, Van Dyke T. (2009). Aurora-A kinase is essential for bipolar spindle formation and early development. Mol Cell Biol. 29, 1059-1071.
Rivera-Perez, J. A. (2007). Axial specification in mice: Ten years of advances and controversies. J. Cell. Physiol. 213, 654-660.
Rivera-Perez JA, Diefes H, Magnuson T. (2007). A simple enzymatic method for parietal yolk sac removal in early postimplantation mouse embryos.
Dev. Dyn. 236:489-93.
Rivera-Pérez, J. A. and Magnuson T. (2005). Primitive streak formation in mice is preceded by localized activation of Brachyury and Wnt3. Dev. Biol. 288, 363-371.
Abell, A. N., Rivera-Pérez, J. A., Cuevas, B. D., Uhlik, M. T., Sather, S., Johnson, N. L., Minton, S. K., Lauder, J. M., Morrison, J. A., Showell, C., Conlon, F. L., Godfrey, V. L., Magnuson, T., Vaillancourt, R. R., Heasley, L. E. and Johnson, G. L. (2005). Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryo. Mol. Cell. Biol. 20, 8948-8959.
Rivera-Pérez, J. A., Mager, J. and Magnuson, T. (2003). Dynamic morphogenetic events characterize the mouse visceral endoderm. Dev. Biol. 270, 470-487.
Camus, A., Davidson, B. P., Billiards, S., Khoo, P-L., Rivera-Pérez, J. A., Wakamiya, M., Behringer, R. R. and Tam, P. P. L. (2000). The morphogenetic role of the midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo. Development 127, 1799-1813.
Rivera-Pérez, J. A., Wakamiya, M. and Behringer, R. R. (1999). Gossecoid acts cell-autonomously in mesenchyme-derived tissues during craniofacial development. Development 126, 3811-3821.
Wakamiya, M., Lindsay, E. A., Rivera-Pérez, J. A., Baldini, A. and Behringer, R. R. (1998). Functional analysis of Gscl in the pathogenesis of the DiGeorge and Velocardiofacial syndromes. Amer. J. Hum. Genet. 7, 1835-1840.
Wakamiya, M., Rivera-Pérez, J. A., Baldini, A. and Behringer, R.R. (1997). Goosecoid and Goosecoid related genes in mouse embryogenesis. Cold Spring Harb. Symp. Quant. Biol. 62, 145-149.
Filosa, S., Rivera-Pérez, J. A., Perea-Gómez, A., Gansmuller, A., Sasaki, H., Behringer, R. R. and Ang S.-L. (1997) Goosecoid and HNF3-b genetically interact to regulate neural tube patterning during mouse embryogenesis. Development 124, 2843-2854.
Rivera-Pérez, J. A.; Mallo, M.; Gendron-Maguire, M.; Gridley, T. and Behringer, R. R. (1995). Goosecoid is not an essential component of the mouse gastrula organizer but is required for craniofacial and rib development. Development 121, 3005-3012.
Hasty, P., Rivera-Pérez J. A. and Bradley A. (1995). Gene conversion during vector insertion in embryonic stem cells. Nucl. Acids Res. 23, 2058-2064.
Rivera-Pérez, J. A., Rojas-Martínez, A., Charles-García, F. and Barrera-Saldaña, H. A. (1993). Analisis molecular de la hemofilia en familias del noreste de México. Rev. Inv. Clin. 45, 23-28.
O'Neal, W. K.; Hasty, P.; Mc Gray, P. B.; Casey, B.; Rivera-Pérez, J. A.; Welsh, M. J.; Beaudet, A. L. and Bradley, A. (1993). A severe phenotype in mice with a duplication of exon 3 in the cystic fibrosis locus. Hum. Mol. Genet. 2, 1561-1569.
Ramírez-Solis, R., Rivera-Pérez, J. A., Wallace, J. D., Wims, M. and Bradley, A. (1992). Genomic DNA microextraction: A method to screen numerous samples. Anal. Biochem. 201, 331-335.
Hasty, P., Rivera-Pérez, J. A. and Bradley, A. (1992). The role and fate of DNA ends for homologous recombination in embryonic stem cells. Mol. Cell. Biol. 12, 2464-2474.
Hasty, P., Rivera-Pérez, J. A. and Bradley, A. (1991). The length of homology required for gene targeting in embryonic stem cells. Mol. Cell. Biol. 11, 5586-5591.
Hasty, P., Rivera-Pérez, J. A., Chang, C., and Bradley, A. (1991). Target frequency and integration pattern for insertion and replacement vectors in embryonic stem cells. Mol.Cell. Biol. 11, 4509-4517.
Rotations Available
1. Role of Wnt genes in early embryogenesis. Multiple Wnt genes are expressed during gastrulation in mice and one of them Wnt3 is essential for gastrulation. Wnt3 mutants fail to produce a primitive streak and die shortly thereafter. This project will analyze the interactions between Wnt3 and other Wnt genes taking advantage of Wnt3 mutant embryos.
2. Isolation of epiblast stem cells and induced pluripotent stem cells. The aim of this project is to isolate epiblast stem cells (EpiSC) and induced pluripotent stem (iPS) cells to study patterning mechanisms in early embryogenesis.
Academic Background
Jaime Rivera received his B.Sc. in Biology from the Universidad Autónoma de Nuevo León, in Monterrey, México in 1990. He obtained his Ph.D. from the University of Texas at Houston in 1997 under the direction of Richard Behringer. He then pursued his post-doctoral training with Terry Magnuson first at Case Western Reserve University and later at the University of North Carolina at Chapel Hill. He joined the faculty in the Department of Cell Biology at the University of Massachusetts Medical School in August 2006.
Office: S7-228
Phone: 508-856-4189
E-mail: Jaime.Rivera@umassmed.edu
Keywords:
Transgenic Mice,
Cell Dynamics,
Mouse Genetics,
Developmental Biology
Postdoctoral Position Available
Post-Doctoral Position Available
A post-doctoral position is available to conduct studies in this laboratory. Please contact Dr. Jaime Rivera for more information.
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