Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development
Intercellular interactions among cardiac cell populations are essential for cardiac morphogenesis, yet the molecular mechanisms orchestrating these events remain incompletely understood. Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse, is a core planar cell polarity protein w...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/11/774 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849330593325645824 |
|---|---|
| author | Kathryn Byerly Cayla Wolfe Hannah Parris Charlotte Griggs Emily Wilson Matthew Huff Molly Griggs Jordan Morningstar Lilong Guo Fulei Tang Jan Guz Taylor Petrucci Ranan Phookan Brian Loizzi Cortney Gensemer Russell A. Norris |
| author_facet | Kathryn Byerly Cayla Wolfe Hannah Parris Charlotte Griggs Emily Wilson Matthew Huff Molly Griggs Jordan Morningstar Lilong Guo Fulei Tang Jan Guz Taylor Petrucci Ranan Phookan Brian Loizzi Cortney Gensemer Russell A. Norris |
| author_sort | Kathryn Byerly |
| collection | DOAJ |
| description | Intercellular interactions among cardiac cell populations are essential for cardiac morphogenesis, yet the molecular mechanisms orchestrating these events remain incompletely understood. Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse, is a core planar cell polarity protein whose function in the developing heart has not been fully elucidated. To address this, we generated a Dchs1-HA knock-in mouse model to define its spatial, temporal, and cellular expression patterns. Using immunohistochemistry, western blotting, and single-cell transcriptomics across developmental stages, we demonstrate that cardiac Dchs1 expression is restricted to non-cardiomyocyte lineages. DCHS1 displays dynamic subcellular localization and tissue organization depending on the developmental timepoint, with staining being found in epicardial and endocardial surfaces at earlier embryonic stages and in the compact myocardium in later fetal and neonatal stages. During fetal and neonatal stages, DCHS1-positive non-myocyte, non-endothelial cells form polarized extensions that bridge endothelial and non-myocyte, non-endothelial cells, suggesting direct heterotypic and homotypic interactions. Western blotting revealed evidence of DCHS1 proteolytic cleavage, with intracellular C-terminal fragments. RNA co-expression with its binding partner FAT4 supports a conserved, non-myocyte-specific DCHS1-FAT4 signaling axis. These findings identify DCHS1 as a potential molecular tether that is utilized in intercellular communications during cardiac development, with implications for congenital and acquired heart disease. |
| format | Article |
| id | doaj-art-684cf69c73984101b1006ddf103e7d22 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-684cf69c73984101b1006ddf103e7d222025-08-20T03:46:52ZengMDPI AGCells2073-44092025-05-01141177410.3390/cells14110774Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac DevelopmentKathryn Byerly0Cayla Wolfe1Hannah Parris2Charlotte Griggs3Emily Wilson4Matthew Huff5Molly Griggs6Jordan Morningstar7Lilong Guo8Fulei Tang9Jan Guz10Taylor Petrucci11Ranan Phookan12Brian Loizzi13Cortney Gensemer14Russell A. Norris15Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Comparative Medicine, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Comparative Medicine, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USAIntercellular interactions among cardiac cell populations are essential for cardiac morphogenesis, yet the molecular mechanisms orchestrating these events remain incompletely understood. Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse, is a core planar cell polarity protein whose function in the developing heart has not been fully elucidated. To address this, we generated a Dchs1-HA knock-in mouse model to define its spatial, temporal, and cellular expression patterns. Using immunohistochemistry, western blotting, and single-cell transcriptomics across developmental stages, we demonstrate that cardiac Dchs1 expression is restricted to non-cardiomyocyte lineages. DCHS1 displays dynamic subcellular localization and tissue organization depending on the developmental timepoint, with staining being found in epicardial and endocardial surfaces at earlier embryonic stages and in the compact myocardium in later fetal and neonatal stages. During fetal and neonatal stages, DCHS1-positive non-myocyte, non-endothelial cells form polarized extensions that bridge endothelial and non-myocyte, non-endothelial cells, suggesting direct heterotypic and homotypic interactions. Western blotting revealed evidence of DCHS1 proteolytic cleavage, with intracellular C-terminal fragments. RNA co-expression with its binding partner FAT4 supports a conserved, non-myocyte-specific DCHS1-FAT4 signaling axis. These findings identify DCHS1 as a potential molecular tether that is utilized in intercellular communications during cardiac development, with implications for congenital and acquired heart disease.https://www.mdpi.com/2073-4409/14/11/774Dachsouscadherincardiac developmentcell polarity |
| spellingShingle | Kathryn Byerly Cayla Wolfe Hannah Parris Charlotte Griggs Emily Wilson Matthew Huff Molly Griggs Jordan Morningstar Lilong Guo Fulei Tang Jan Guz Taylor Petrucci Ranan Phookan Brian Loizzi Cortney Gensemer Russell A. Norris Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development Cells Dachsous cadherin cardiac development cell polarity |
| title | Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development |
| title_full | Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development |
| title_fullStr | Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development |
| title_full_unstemmed | Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development |
| title_short | Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development |
| title_sort | dynamic expression and functional implications of the cell polarity gene dchs1 during cardiac development |
| topic | Dachsous cadherin cardiac development cell polarity |
| url | https://www.mdpi.com/2073-4409/14/11/774 |
| work_keys_str_mv | AT kathrynbyerly dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT caylawolfe dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT hannahparris dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT charlottegriggs dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT emilywilson dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT matthewhuff dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT mollygriggs dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT jordanmorningstar dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT lilongguo dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT fuleitang dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT janguz dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT taylorpetrucci dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT rananphookan dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT brianloizzi dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT cortneygensemer dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment AT russellanorris dynamicexpressionandfunctionalimplicationsofthecellpolaritygenedchs1duringcardiacdevelopment |