Biology subjects

Sako, K.

Publications and source records attributed to Sako, K..

5 recordsLinked to original sources

bioRxiv2025

Endothelial-zippering proceeds by sensing heartbeat-driven force through Cadherin-6 during heart-vessel connection in zebrafish

The connection between the heart and great vessels established during embryogenesis is essential for circulation. However, how great veins adhere to the endocardium lining the inside lumen of the beating heart remains unknown. Here, using zebrafish, we demonstrate that the endocardium and great veins are sealed in a zipper-closing manner outside the beating heart. The gradual elongation of the endocardium, driven by convergent extension, organized this adhesion by pulling venous ECs along the anterior-posterior axis. Time-specific manipulation of the heart rate revealed that this endocardial elongation proceeds against heartbeat-driven force. From time-lapse imaging of adherens junctions, which would counterbalance mechanical forces, we found a specific contribution of Cadherin-6 instead of Cadherin-5 in sensing endocardium-specific mechanical force. This specificity was confirmed by the depletion of Cadherin-6 that caused endocardium deformation. Altogether, we propose Cadherin-6 mediated EC-zippering as a novel mechanism that updates the understanding of Cadherin usage in dynamic morphogenesis.

developmental biology↗

bioRxiv2025

Chemokine induces phase transition from non-directional to directional migration during angiogenesis

During angiogenesis, sprouting endothelial cells (ECs) migrate and eventually connect to target vessels to form new vessel branches. However, it remains unclear how these sprouting vessels migrate toward the target vessels in three-dimensional space. We performed in vivo imaging of the cerebral capillary network formation in zebrafish to investigate how sprouting tip cells migrate toward their targets. Of note, we found that tip cells reach the target vessels through two phases: a non-directional phase and a directional phase. In the non-directional phase, sprouting tip cells dynamically extend and retract their protrusions at the leading front and have less directionality in their movement. In contrast, once tip cells enter the directional phase, they migrate directly toward the anastomotic targets. Chemokine receptor Cxcr4a and its ligand Cxcl12b are important for the phase transition to the directional phase. In cxcr4a mutants, sprouting tip cells lose their directionality and tend to connect to nearby sprouting ECs, resulting in altered capillary network patterning. Furthermore, in wild-type (WT) larvae, local Ca2+ oscillations were detected in protrusions of tip cells, specifically in the non-directional phase, but almost disappeared in the directional phase as a result of the Cxcr4-dependent phase transition. Thus, this study provides evidence of a chemokine-induced phase transition in migrating tip cells, which is important for proper vascular network formation in the zebrafish brain.

cell biology↗

bioRxiv2023

Angpt1 binding to Tie1 regulates the signaling required for lymphatic vessel development in zebrafish

Development of the vascular system is regulated by multiple signaling pathways mediated by receptor tyrosine kinases (RTKs). Among them, Angiopoietin (Ang)/Tie signaling regulates lymphatic and blood vessel development in mammals. Of the two Tie receptors, Tie2 is well known as a key mediator of Ang/Tie signaling, but unexpectedly, recent studies reveal that the Tie2 locus has been lost in many vertebrate species, while the Tie1 gene is more commonly present. However, Tie1-driven signaling pathways, including ligands and cellular functions, are not well understood. Here, we performed comprehensive mutant analyses of Angiopoietins and Tie receptors in zebrafish and found that only angpt1 and tie1 mutants show defects in trunk lymphatic vessel development. Among zebrafish Angiopoietins, only Angpt1 binds to Tie1 as a ligand. We indirectly monitored Ang1/Tie1 signaling and detected Tie1 activation in sprouting endothelial cells (ECs), where Tie1 inhibits nuclear import of EGFP-Foxo1a. Angpt1/Tie1 signaling functions in EC migration, proliferation, and lymphatic specification during early lymphangiogenesis, at least in part by modulating Vegfc/Vegfr3 signaling. Thus, we show Angpt1/Tie1 signaling to constitute an essential signaling pathway for lymphatic development in zebrafish. Brief Summary StatementZebrafish Angpt1/Tie1 signaling is characterized as an essential signaling pathway for trunk lymphatic development, with Tie1 regulating Foxo1 localization and modulating Vegfc/Vegfr3 signaling.

developmental biology↗

bioRxiv2020

Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis

Zygotic genome activation (ZGA) initiates regionalized transcription responsible for the acquisition of distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, whether the tissue-specific transcription is mechanistically linked with the onset of ZGA is unknown. Here, we have addressed the involvement of chromatin organizer SATB2 in orchestrating these processes during vertebrate embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility revealed contrasting molecular functions of maternal and zygotic pools of Satb2. Maternal Satb2 represses zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented. We discuss the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.

developmental biology↗

bioRxiv2019

Periosteum-derived Osteocrin regulates bone growth through both endochondral ossification and intramembranous ossification

During development of long bones, two mechanistically distinct processes contribute to long- and short-axis growth. Endochondral ossification in the growth plate leads to the long-axis growth, while intramembranous ossification including apposition in the periosteum regulates the short axis growth. Here, we show that periosteal osteoblast-derived secretory peptide, Osteocrin (OSTN), promotes both types of long bone growth through potentiation of signaling by C-type natriuretic peptide (CNP), because OSTN inhibits the clearance of CNP by binding to natriuretic peptide receptor 3 (NPR3). The mice lacking OSTN showed less bone mass in trabecular and cortical regions than the control mice, suggesting the dual functions of OSTN in long bone growth. We found that OSTN regulated trabecular bone formation by inducing proliferation and maturation of chondrocytes possibly through enhancing CNP-dependent signaling. Besides the contribution of OSTN to long axis growth, we demonstrated that OSTN together with CNP induced osteoblast differentiation of periosteum-derived multipotent progenitor cells expressing NPR3. These data suggest that OSTN induces long bone growth through endochondral ossification and osteoblast specification of multipotent progenitor cells in the periosteum.

developmental biology↗