Cell and Developmental Biology University of Michigan

Surprisingly little is known about the molecular histogenesis of the mammalian CNS, due in part to the inaccessibility of the early embryo for direct manipulation. Our research has focused on the role of the BMP signaling cascade in this process using embryonic stem (ES) cells as a model of the events involved in lineage segregation, followed by studies in the intact embryo.

Since the gene expression profile of ES cells is similar to the inner cell mass and the epiblast and they are poised to undergo multi-lineage differentiation, ES cells can be a powerful model system to tease out the successive waves of gene expression and inhibition that shape the early embryo. Our research is focused on the very early histogenesis of the primitive nervous system.

Publications

Representative Publications

• Gratsch TE, O’Shea KS. Noggin and chordin have distinct activities in promoting lineage commitment of mouse embryonic stem (ES) cells. Developmental Biology 2002, 245: 83-94.
• Velkey JM, O’Shea KS. Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. genesis, 2003, 37: 18-24.
• O’Shea KS. Models for neural development and clinical disorders, In: Bottenstein J (Ed), Neural Stem Cells: Development and Transplantation. New York: Kluwer Publishers, 2003, pp 1-54.
• Gratsch TE, De Boer LS, O’Shea KS. RNA interference of BMP-4 gene expression in postimplantation mouse embryos. genesis, 2003, 37: 12-17.
• Lorincz MT , Detloff PJ, Albin RL, O’Shea KS. Embryonic stem cells expressing expanded CAG repeats undergo aberrant neuronal differentiation and have persistent Oct-4 and REST/NRSF expression. Molecular and Cellular Neuroscience, 2004, 26: 135-143.
• O’Shea KS. MINIREVIEW: Self-renewal vs differentiation of mouse embryonic stem cells. Biology of Reproduction, 2004, in press.