HAND2-mediated epithelial maintenance and integrity in cardiac outflow tract morphogenesis
| Autor: | Hengwei Jin, Meng Xia, Zhongzhou Yang, Wen Luo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Morphogenesis
Mice Transgenic Biology Epithelium Adherens junction 03 medical and health sciences Mice 0302 clinical medicine Pregnancy Cell polarity Basic Helix-Loop-Helix Transcription Factors Animals Humans Cell adhesion Molecular Biology Actin Cells Cultured 030304 developmental biology 0303 health sciences Myocardium Cell Polarity Gene Expression Regulation Developmental Cell Differentiation Heart Actin cytoskeleton Embryo Mammalian Outflow tract morphogenesis Cell biology HEK293 Cells Contractile fiber Female 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Zdroj: | Development (Cambridge, England). 146(13) |
| ISSN: | 1477-9129 |
| Popis: | During embryogenesis, epithelial organization is the prerequisite for organogenesis, in particular, for establishing the tubular structure. Recent studies provided hints about epithelial formation in early heart development, which has not been systemically explored. Here, we revealed a gradient of HAND2 protein in the cardiac progenitors in the anterior dorsal pericardial wall (aDPW) and adjacent transition zone (TZ) in the outflow tract (OFT). Deletion of Hand2 caused cell arrest and accumulation in the TZ leading to defective morphogenesis. While apicobasal cell polarity was unaffected, the key epithelial elements of adherens junction and cell-matrix adhesion were disrupted in the TZ of Hand2 mutant mice, indicating poorly formed epithelium. RNA-seq analysis revealed altered regulation of the contractile fiber and actin cytoskeleton, which affected cardiomyocyte differentiation. Furthermore, we have identified Stars as being transcriptionally controlled by HAND2. STARS facilitates actin polymerization that is essential for anchoring the adhesive molecules to create cell adhesion. Thus, we have uncovered a new function of HAND2 in mediating epithelial maintenance and integrity in OFT morphogenesis. Meanwhile, this study provides insights to understanding cardiac progenitor contribution to OFT development. |
| Databáze: | OpenAIRE |
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