Hometown: Belem, Brazil

Alma Mater: Federal University of Para Brazil, Biology

Impact of calcium modulation in organ laterality

The external bilateral symmetry of vertebrates contrasts with the asymmetric placement of most internal organs with respect to the left-right (L-R) axis. Proper L-R patterning cues are essential for organ morphogenesis, as perturbations to L-R signaling pathways can result in a wide spectrum of malformations, including heart defects. L-R axis determination require asymmetric gene expression, which appears to be controlled by a ciliated structure known as the mouse and chick nodes and the Kupffer’s Vesicle (KV) in zebrafish.

The zebrafish KV is derived from the dorsal forerunner cells (DFCs), a compact cluster of cells, which migrate ahead of the blastoderm during . Several genes expressed in the DFCs are involved in L-R patterning. I have identified endogenous Ca 2+ release in the DFC region, prior to KV formation, and transient inhibition of this Ca 2+ release activity results in altered L-R patterning. Analysis of the molecular and cellular responses to Ca 2+ inhibition revealed increased ß-catenin stability and subsequent impact in DFC clustering in the tailbud.

In addition we define a DFC-like cell population in Xenopus and demonstrate a similar Ca 2+ sensitive stage resulting in ectopic nuclear β-catenin and altered laterality. Our data demonstrate a key, early role for intracellular Ca 2+ activity prior to somitogenesis. My future studies will focus on investigating how early Ca 2+ activity directs DFC migration/cohesion and proper L-R patterning.

Publications:

Zhang Y, Yeh JR, Mara A, Ju R, Hines JF, Cirone P, Griesbach HL, Schneider I, Slusarski DC, Holley SA, Crews CM. A chemical and genetic approach to the mode of action of fumagillin. Chem Biol. 2006 Sep;13(9):1001-9.