Cdc42 activity drives fate specification of the heart lineage

Meeting Abstract

15.10  Monday, Jan. 4  Cdc42 activity drives fate specification of the heart lineage. WHITAKER, Stacia E.*; COOLEY, James; SWEENEY, Sarah; DAVIDSON, Brad; University of Arizona; University of Arizona; University of Arizona; University of Arizona

The establishment of polarity and subsequent asymmetric cell division are required for differentiation throughout development. In Ciona intestinalis, such a division occurs in the heart founder cells, with each of four founders giving rise to a small heart progenitor cell and a larger tail muscle cell. Although FGF signaling occurs prior to division, ERK is activated only in the smaller daughter and results in heart cell-specific behaviors such as migration and proliferation. The underlying cause of differential ERK activation in response to FGF in the heart lineage is not yet understood. The Rho GTPase Cdc42 has been shown to influence both size and fate asymmetry in many systems. To determine whether Cdc42 is involved in the establishment of polarity in the Ciona heart lineage, we used wild type and signaling-active Cdc42 constructs expressed under the heart founder-specific Mesp enhancer. We found that Cdc42 activity promotes migration. To distinguish between effects on actin dynamics and cell fate, we employed the FoxF reporter construct as a heart cell marker. Our data shows that constitutive activity of Cdc42 results in a switch from tail muscle to heart cell fate, as well as disruption of size asymmetry. Cdc42 has a multitude of interactors that regulate actin dynamics, receptor endocytosis, polarity, and signal propagation. Polarized stabilization of the FGF receptor or differential transport may result in propagation of the FGF/MAPK signal in the heart progenitor. To further characterize Cdc42’s role in establishing polarity, we will employ Cdc42 mutants that bind its effectors selectively.

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