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Karling Lecture: “Shaping and Signaling Mechanism of a BMP Morphogen Gradient”

Purdue Institute for Integrative Neuroscience
April 9, 2018
4:00 PM - 5:00 PM
MJIS 1001

Description

Mary C. Mullins Ph.D., Professor of Cell and Developmental Biology, Perelman School of Medicine

Topic: “Shaping and Signaling Mechanism of a BMP Morphogen Gradient”

The vertebrate embryonic dorsoventral (DV) axis is patterned by a bone morphogenetic protein (BMP) activity gradient during gastrulation. Although postulated, this gradient had not been previously visualized at high resolution. We quantified in every cell of the embryo using automated algorithms the nuclear intensities of phosphorylated-Smad5 (P-Smad) protein, the BMP signal transducing protein. The quantitative dynamics of the gradient will be presented, as well as the role of extracellular modulators in shaping the gradient. A mathematical model-based computational screen was then generated by our collaborator David Umulis (Purdue University) to test hypotheses for gradient formation. This systems biology approach revealed an unexpected mechanism, that of a source-sink, upturning the widespread held BMP antagonist counter-gradient model. In other studies, we found that a Bmp2-Bmp7 heterodimer signals exclusively in DV patterning in the zebrafish. In many biological contexts, BMP heterodimers have more potent signaling activity. Our progress in elucidating the BMP heterodimer signaling mechanism will also be presented.

Reception starting at 3:30 PM

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