ABSTRACT
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 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. Although 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. In addition, this study also provides insights for understanding cardiac progenitor contribution to OFT development.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: Z.Y., W.L.; Methodology: M.X., H.J.; Formal analysis: Z.Y.; Investigation: M.X., W.L., H.J.; Writing - original draft: M.X.; Writing - review & editing: Z.Y.; Supervision: Z.Y.; Project administration: Z.Y.
Funding
This work was supported by grants from the National Natural Science Foundation of China (31571490, 81741003, 91519312, 91854111 and 31130037), the National Key Basic Research Program of China (2012CB966600) and the State Key Laboratory of Genetic Engineering of Fudan University (SKLGE-1604) to Z.Y.
Data availability
RNA-seq data have been deposited in GEO under accession number GSE131362.
Supplementary information
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.177477.supplemental
- Received February 27, 2019.
- Accepted June 3, 2019.
Log in using your username and password
Log in through your institution
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$30.00 .
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
Keywords
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Subject collections
Other journals from The Company of Biologists
Special Issue: development at the single cell level
Our Special Issue on single cell approaches to developmental biology contains a wealth of content, from research papers using various model systems to the latest cutting edge techniques and a selection of reviews and commentaries surveying the field and its future.
Meet New York-based Eduardo Leyva-Díaz and Oliver Hobert, authors of a recent Development paper on transcriptional autoregulation in C. elegans.
Meet the team
The Development team are going to be out and about through June and July. Do come and meet them! Going to the Gordon conference on Developmental Biology in South Hadley, USA, June 16 – 21? Meet our Executive Editor Katherine Brown. At the ISSCR 2019: The global stem cell event in Los Angeles, 26-29 June you can meet Senior Editor Seema Grewal. Reviews Editor Alex Eve and Online Editor Aidan Maartens will be at the SDB 78th Annual Meeting in Boston, USA, July 26-30.
The Company of Biologists Workshops - Chromatin-Based Regulation of Development
Watch a short video from this workshop, where we discussed what mechanisms related to chromatin biology inform developmental processes, explored plans to integrate unsolved developmental questions with exciting new avenues in chromatin biology, and which outstanding questions in gene regulation might be best revealed in the context of dynamic cell fate transitions. Find out about upcoming workshops here.
Are TAD borders that important to prevent enhancer rewiring? preLighter Jesus Victorino highlights a preprint by Wendy Bickmore and Laura Lettice’s team which shows that tissue-specific enhancers maintain robust control of Shh gene expression after challenging the architectural chromatin context.
Catch up with other recent preLights selected for the developmental biology community.
Articles of interest in our sister journals
Rho kinase-dependent apical constriction counteracts M-phase apical expansion to enable mouse neural tube closure
Max B. Butler, Nina E. Short, Eirini Maniou, Paula Alexandre, Nicholas D. E. Greene, Andrew J. Copp, Gabriel L. Galea
Journal of Cell Science
Suppressor of Fused regulates the proliferation of postnatal neural stem and precursor cells via a Gli3-dependent mechanism
Hector G. Gomez, Hirofumi Noguchi, Jesse Garcia Castillo, David Aguilar, Samuel J. Pleasure, Odessa R. Yabut
Biology Open