Metal transporter Slc30a1 controls pharyngeal neural crest differentiation via the zinc‐Snai2‐Jag1 cascade

Abstract

The pharyngeal arch (PA) is a neural crest (NC)‐derived organ that is transiently developed during embryogenesis and is required for the subsequent development of various tissues. However, the role of zinc during PA differentiation from NC progenitor cells is unknown. Here, we found that the metal transporters Slc30a1a and Slc30a1b mediate zinc homeostasis during PA differentiation. Slc30a1‐deficient zebrafish develop zinc accumulation in NC cells, with increased expression of stemness markers and PA dorsal genes, and SMART‐seq analyses revealed that the genes snai2 and jag1b may serve as downstream targets. Furthermore, functional studies showed that knocking down either snai2 or jag1b rescues PA development in Slc30a1‐deficient zebrafish. Notably, we identified the double zinc‐finger domain in the transcription factor Snai2 as a zinc‐responsive element that regulates jag1b expression. Our findings indicate that the Slc30a1/zinc‐ snai2 ‐ jag1b axis is an essential regulatory network controlling PA differentiation, shedding new light on the function of zinc homeostasis in maintaining NC cell stemness and multipotency in vertebrates.

Revealing the Role of Zinc Ions in Atherosclerosis Therapy via an Engineered Three‐Dimensional Pathological Model

“…The downregulated cell proliferation and cell adhesion cause apoptosis, as demonstrated in Section 2.3. [ 34 ] However, cell motility, cell proliferation, and cell adhesion exhibited significantly upregulated after zinc ion treatment at the concentration of 20.0 µ m ( P < 0.05), which testified to the CCK‐8 results as well as the growth‐promoting effect on cells (Figure 8I). Moreover, the signal transduction was significantly upregulated in the group of zinc ion treatment at the concentration of 116.2 µ m compared with the engineered 3D AS model, implying the potential abnormal signaling and thereby reduced cell activity (Figure 8J).…”

“…PCA indicated all merged proteomics in individual datasets with clear class separation and accounted for 38.8% of the variance in gene expression, demonstrating the profound changes and independent gene expression in each group due to the stimulation of pathological factors and zinc ion treatments ( Figure A). [ 34 ] In addition, individual groups exhibited consistent and distinct changes when comparing samples in terms of both global protein expressions (Figure 8B). Overall, a consistent decrease in the global protein was observed (Figure 8C,D).…”

“…Notably, SLC30A1 is expressed at the cell membrane and encodes a putative zinc transporter. [ 34 ] Besides that, significant downregulation of HMOX1 was involved ( P < 0.05). Some researchers found that the HMOX1 inhibitor could significantly alleviate the occurrence and development of ferroptosis in mouse hearts and thus protect cardiac function.…”

Intestinal precursors avoid being misinduced to liver cells by activating Cdx-Wnt inhibition cascade

“…The cdx1b CRISPR and sfrp5 CRISPR mutants in which mutagenesis were targeted at exon 2 and exon 1, respectively, were generated by CRISPR/Cas9 as previously described ( 43 , 44 ). The 20-nt guide RNA (gRNA) target sequences were used as follows: cdx1b exon 2 (5′-ACAGCCGCTACATCACAATA-3′); sfrp5 exon 1 (5′-GGACCACGAGACCATGCCTG-3′).…”