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.

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

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.

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).

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 ofHhex, 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.