Mild cold stress specifically disturbs clustering movement of DFCs and sequential organ left-right patterning in zebrafish

Abstract

In poikilothermic animals, the distinct acclimatization ability of different organs has been previously addressed, while the tissue-specific role of cold stress in early development is largely unknown. In this study, we discovered that despite its role in delaying embryonic development, mild cold stress (22°C) does not disturb multiple-organ progenitor specification, but does give rise to organ left-right (LR) patterning defects. Regarding the mechanism, the data showed that mild cold stress downregulated the expression of cell-adhesion genes cdh1 and cdh2 during gastrulation, especially in dorsal forerunner cells (DFCs), which partially disturbed the clustering movement of DFCs, Kupffer’s vesicle (KV) morphogenesis, and ciliogenesis. As a result, the defects of KV/cilia disrupted asymmetric nodal signaling and subsequent heart and liver LR patterning. In conclusion, our data novelly identified that, in early development, DFCs are more sensitive to mild cold stress, and mild cold stress repressed the expression of cell adhesion-related gene cdh1 and cdh2. This role partially disturbed the clustering movement of DFCs, which resulted in defective KV/cilia development and sequential organ LR patterning defects.

miR-29a Is Downregulated in Progenies Derived from Chronically Stressed Males

“…We found a diminished survival in larvae from stressed parents accompanied by lower values of hatching rates ( Figure 3 B,C), confirming our in silico data and molecular analyses. Our results agree well with recent research indicating that certain types of direct stress—specifically cold stress—can affect this process of morphogenesis, triggering decreased survival ratios in zebrafish larvae [ 52 ]. In the present work, we determine the same effects on the development, survival, and hatching rates under indirect stress conditions in zebrafish.…”

“…Cell division, differentiation, proliferation, and morphogenesis are coordinated events during zebrafish embryonic development and appear frequently in disarray in different pathologies such as cancer. The role of morphogenesis in zebrafish embryo survival and hatching rates has been widely studied and reviewed [ 50 , 51 , 52 ]. We found a diminished survival in larvae from stressed parents accompanied by lower values of hatching rates ( Figure 3 B,C), confirming our in silico data and molecular analyses.…”

Cdonis required for organ Left-Right patterning via regulating DFCs migration and the sequential ciliogenesis

“…KV develops directional fluid flow and establishes LR signaling, and then breaks down around 18 hpf when KV cells undergo a epithelial to mesenchymal transition (Amack, 2021) and migrate away to incorporate into muscle and notochord (Ikeda et al, 2022). In the past decades, much of genes or environmental elements had been reported to involve in DFCs clustering migration (Ablooglu et al, 2010; Gao et al, 2011; Kajikawa et al, 2022; Lai et al, 2012; Liu et al, 2022), proliferation (Abdel-Razek et al, 2023; Gokey et al, 2015; Liu et al, 2019; Zhang et al, 2012) and the final KV formation and ciliogenesis, while the mechanisms underlying this process are from being completely elucidated.…”

“…Zebrafish wild type (AB), Tg ( cmcl2 :GFP)(Liu et al, 2022), Tg ( fabp10 :GFP)(Liu et al, 2022) and Tg ( sox17 :GFP)(Zhu et al, 2019) lines were maintained at 28.5°C. The embryonic stage was determined according to the external morphology as the standard criteria described before (Kimmel et al, 1995).…”