Extra-embryonic syndecan 2 regulates organ primordia migration and fibrillogenesis throughout the zebrafish embryo. Development

Division of Pediatric Cardiology, University of Utah, Salt Lake City, UT 84112, USA.
Development (Impact Factor: 6.46). 10/2009; 136(18):3143-52. DOI: 10.1242/dev.031492
Source: PubMed


One of the first steps in zebrafish heart and gut organogenesis is the migration of bilateral primordia to the midline to form cardiac and gut tubes. The mechanisms that regulate this process are poorly understood. Here we show that the proteoglycan syndecan 2 (Sdc2) expressed in the extra-embryonic yolk syncytial layer (YSL) acts locally at the YSL-embryo interface to direct organ primordia migration, and is required for fibronectin and laminin matrix assembly throughout the embryo. Surprisingly, neither endogenous nor exogenous sdc2 expressed in embryonic cells can compensate for knockdown of sdc2 in the YSL, indicating that Sdc2 expressed in extra-embryonic tissues is functionally distinct from Sdc2 in embryonic cells. The effects of sdc2 knockdown in the YSL can be rescued by extra-embryonic Sdc2 lacking an extracellular proteolytic cleavage (shedding) site, but not by extra-embryonic Sdc2 lacking extracellular glycosaminoglycan (GAG) addition sites, suggesting that distinct GAG chains on extra-embryonic Sdc2 regulate extracellular matrix assembly, cell migration and epithelial morphogenesis of multiple organ systems throughout the embryo.

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    • "Proper expression of Fn in the microenvironment is crucial for establishing the apicobasal organization that myocardial cells need for their medial migration (Arrington and Yost, 2009; Garavito- Aguilar et al., 2010; Sakaguchi et al., 2006; Trinh and Stainier, 2004; Trinh et al., 2005). Furthermore, S1pr2/Mil has been shown Fig. 7 "
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    ABSTRACT: Coordination between the endoderm and adjacent cardiac mesoderm is crucial for heart development. We previously showed that myocardial migration is promoted by convergent movement of the endoderm, which itself is controlled by the S1pr2/Gα13 signaling pathway, but it remains unclear how the movements of the two tissues is coordinated. Here, we image live and fixed embryos to follow these movements, revealing previously unappreciated details of strikingly complex and dynamic associations between the endoderm and myocardial precursors. We found that during segmentation the endoderm underwent three distinct phases of movement relative to the midline: rapid convergence, little convergence and slight expansion. During these periods, the myocardial cells exhibited different stage-dependent migratory modes: co-migration with the endoderm, movement from the dorsal to the ventral side of the endoderm (subduction) and migration independent of endoderm convergence. We also found that defects in S1pr2/Gα13-mediated endodermal convergence affected all three modes of myocardial cell migration, probably due to the disruption of fibronectin assembly around the myocardial cells and consequent disorganization of the myocardial epithelium. Moreover, we found that additional cell types within the anterior lateral plate mesoderm (ALPM) also underwent subduction, and that this movement likewise depended on endoderm convergence. Our study delineates for the first time the details of the intricate interplay between the endoderm and ALPM during embryogenesis, highlighting why endoderm movement is essential for heart development, and thus potential underpinnings of congenital heart disease. © 2015. Published by The Company of Biologists Ltd.
    Development 09/2015; 142(17). DOI:10.1242/dev.113944 · 6.46 Impact Factor
    • "Original images were colorcoded to reflect the position of cells located at different dz levels relative to the dorso-ventral axis of the embryo, with dorsal z-planes represented in blue, and ventral-in red portions of the spectrum .Supplementary material related to this article can be found online at http:// of bilateral endoderm progenitor populations. These movements resemble those of the cardiac progenitors (Sakaguchi et al., 2006; Arrington and Yost, 2009), However, in natter/fibronectin mutants (Trinh and Stainier, 2004) cardia bifida is observed, yet foregut morphogenesis is not affected, suggesting that endodermal and cardiac progenitors may rely on distinct mechanisms for arrival at the midline. Likewise, Ye and Lin (2013) showed that endodermal S1pr2/Galpha13 signaling, working through a RhoGEF-dependent pathway, drives the convergence of the endoderm to the midline, but not the convergence of the mesoderm. "
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    ABSTRACT: Formation of the muscular layer of the heart, the myocardium, involves the medial movement of bilateral progenitor fields; driven primarily by shortening of the endoderm during foregut formation. Using a combination of time-lapse imaging, microsurgical perturbations and computational modeling, we show that the speed of the medial-ward movement of the myocardial progenitors is similar, but not identical to that of the adjacent endoderm. Further, the extracellular matrix microenvironment separating the two germ layers also moves with the myocardium, indicating that collective tissue motion and not cell migration drives tubular heart assembly. Importantly, as myocardial cells approach the midline, they perform distinct anterior-directed movements relative to the endoderm. Based on the analysis of microincision experiments and computational models, we propose two characteristic, autonomous morphogenetic activities within the early myocardium: 1) an active contraction of the medial portion of the heart field and 2) curling-the tendency of the unconstrained myocardial tissue to form a spherical surface with a concave ventral side. In the intact embryo, these deformations are constrained by the endoderm and the adjacent mesoderm, nevertheless the corresponding mechanical stresses contribute to the proper positioning of myocardial primordia. Copyright © 2015 Elsevier Inc. All rights reserved.
    Developmental Biology 05/2015; 404(1). DOI:10.1016/j.ydbio.2015.04.016 · 3.55 Impact Factor
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    • "Together these lines of evidence indicate that hspb7, and to a lesser extent hspb12, are important in making the YSL capable of supporting precardiac mesoderm migration (Fig. 8B). YSL-specific knockdowns and mutations have previously demonstrated that the YSL drives cardiac migration, through a common pathway that promotes fibronectin expression in the heart field (Arrington and Yost, 2009; Kupperman et al., 2000; Matsui et al., 2007; Osborne et al., 2008; Sakaguchi et al., 2006; Trinh and Stainier, 2004). Notably, knockdown of the small heat shock protein hspb1 (hsp27) results in cardia bifida in Xenopus (Brown et al., 2007), although it does not do so in zebrafish (Tucker et al., 2009). "
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    ABSTRACT: Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left-right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer's vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0 structure, while control embyros have a predominately 9+2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left-right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads causes coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left-right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects.
    Developmental Biology 10/2013; 384(2). DOI:10.1016/j.ydbio.2013.10.009 · 3.55 Impact Factor
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