Dataset Information

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

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.

SUBMITTER: Guo L

PROVIDER: S-EPMC7570242 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Guo Lilong L Glover Janiece J Risner Alyssa A Wang Christina C Fulmer Diana D Moore Kelsey K Gensemer Cortney C Rumph Mary Kate MK Moore Reece R Beck Tyler T Norris Russell A RA

Journal of cardiovascular development and disease 20200817 3

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 ev ...[more]

PMID: 32824435

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Project description:MicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during early cardiac development. By using whole mount in situ hybridization in developing chick embryos, with microRNA-specific LNA probes, we carried out a detailed study of miR-23b, miR-130a, miR-106a, and miR-100 expression during early stages of embryogenesis (HH3 to HH17). We also correlated those findings with putative microRNA target genes by means of mirWalk and TargetScan analyses. Our results demonstrate a dynamic expression pattern in cardiac precursor cells from the primitive streak to the cardiac looping stages for miR-23b, miR-130a, and miR-106a. Additionally, miR-100 is later detectable during cardiac looping stages (HH15-17). Interestingly, the sinus venosus/inflow tract was shown to be the most representative cardiac area for the convergent expression of the four microRNAs. Through in silico analysis we revealed that distinct Hox family members are predicted to be targeted by the above microRNAs. We also identified expression of several Hox genes in the sinus venosus at stages HH11 and HH15. In addition, by means of gain-of-function experiments both in cardiomyoblasts and sinus venosus explants, we demonstrated the modulation of the different Hox clusters, Hoxa, Hoxb, Hoxc, and Hoxd genes, by these microRNAs. Furthermore, we correlated the negative modulation of several Hox genes, such as Hoxa3, Hoxa4, Hoxa5, Hoxc6, or Hoxd4. Finally, we demonstrated through a dual luciferase assay that Hoxa1 is targeted by miR-130a and Hoxa4 is targeted by both miR-23b and miR-106a, supporting a possible role of these microRNAs in Hox gene modulation during differentiation and compartmentalization of the posterior structures of the developing venous pole of the heart.

Dataset Information

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

Publications

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

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