B.S., 1970

Ph.D., Indiana University 1976

Postdoctoral Fellow, M.I.T. 1976-1980

Assistant Professor, University of Virginia 1980-1988

Associate Professor, University of Miami 1988-1997

Professor, University of Miami 1997-present

 

Cell Fate Determination in the Embryo; mRNA Localization in Oocytes 

My laboratory studies how cell fate is determined in the early Xenopus embryo. Our work has shown that the localization of a small number of mRNAs to one pole of the future egg is critical to normal development. Proteins encoded by these localized mRNAs influence gene expression and cell fate decisions. The cells that will eventually give rise to the gametes, the primordial germ cells, comprise the first cell lineage to be specified by localized mRNAs. Only the germ cell lineage has a program of differentiation that maintains totipotency, or the ability to give rise to all other cell types. Discovering how the germline is initially specified and develops separate from the somatic cell lineages is a fundamental problem. Our long-term goals are to:

1) understand how precursors to the germ cells retain developmental totipotency 

2) characterize the RNA transport systems involved in their localization.

We have isolated mRNAs localized exclusively to primordial germ cells. Remarkably, two of these RNAs, Xcat-2 (related to nanos1) and Xdazl (in DAZ family) are highly conserved and found in the germline of humans and Drosophila. Xdazl and Xcat2/nanos1 encode RNA binding proteins and likely regulate the expression of specific mRNAs. We are interested in identifying these mRNA targets and their function in germ cell development. We know that Xdazl function is essential because anti-sense depletion of Xdazl RNA results in their failure to initiate migration to the gonads. Xcat2/nanos1 is also required and can act as a potent repressor of transcription and translation. Mis-expression of Xcat2 in somatic cells leads to profound abnormal development. Our current hypothesis is that Xcat2/nanos1 is essential for the germline to retain totipotency. 

How the correct mRNAs are localized to the correct locations in the egg is a fascinating problem. Germ line mRNAs localize by a diffusion/entrapment mechanism. We have identified the RNA signal required for proper localization of Xcat-2. Now we are working to isolate the proteins that bind these localization signals. Together, our studies will determine how molecular polarity is established in the oocyte and how this leads to cell fate decisions in the early embryo.