Dynamic Expression Profiles of β-Catenin during Murine Cardiac Valve Development.

Lilong Guo,Reece Moore,Tyler Beck,Janiece Glover,Cortney Gensemer,Russell A Norris,Diana Fulmer,Alyssa Risner,Mary Kate Rumph,Christina Wang,Kelsey Moore

doi:10.3390/jcdd7030031

Abstract

β-catenin has been widely studied in many animal and organ systems across evolution, and gain or loss of function has been linked to a number of human diseases. Yet fundamental knowledge regarding its protein expression and localization remains poorly described. Thus, we sought to define whether there was a temporal and cell-specific regulation of β-catenin activities that correlate with distinct cardiac morphological events. Our findings indicate that activated nuclear β-catenin is primarily evident early in gestation. As development proceeds, nuclear β-catenin is down-regulated and becomes restricted to the membrane in a subset of cardiac progenitor cells. After birth, little β-catenin is detected in the heart. The co-expression of β-catenin with its main transcriptional co-factor, Lef1, revealed that Lef1 and β-catenin expression domains do not extensively overlap in the cardiac valves. These data indicate mutually exclusive roles for Lef1 and β-catenin in most cardiac cell types during development. Additionally, these data indicate diverse functions for β-catenin within the nucleus and membrane depending on cell type and gestational timing. Cardiovascular studies should take into careful consideration both nuclear and membrane β-catenin functions and their potential contributions to cardiac development and disease.

Highlights

The basic protein organization of β-catenin consists of an amino terminal domain, a central region consisting of twelve Armadillo repeats and a carboxyl-terminal region [14,15]
Following Wnt ligand stimulation, β-catenin displaces these transcriptional co-repressors and promotes LEF1 transcription factor activity to regulate a host of functions, including endothelial-to-mesenchymal transformation, proliferation and differentiation
Gain and loss of function studies in the heart have revealed a critical role for β-catenin in cardiac development, especially related to valve morphogenesis [43,44]

Summary

Introduction

As our work has previously focused on the role of the atypical cadherin, DCHS1, and how it can impact valve structure and function through stabilizing adherens junctions [57], we wished to explore the role of the well-studied adherens junction protein, β-catenin and determine whether its expression correlates to the above-described morphogenetic events (shown in Figure 1) during valve development. A more thorough characterization of the expression and localization of either nuclear or membrane β-catenin throughout cardiac development has yet to be reported. A similar spatial pattern of β-catenin expression on the membrane is observed within the outflow tract mesenchyme of the semilunar valves.

Results

Conclusion