Deciphering the cellular and molecular landscapes of Wnt/β-catenin signaling in mouse embryonic kidney development

Hui Zhao1, Hui Gong2, Peide Zhu3

  • 1Guangzhou National Laboratory, Guangzhou International Bio Island, No. 9 Xing Dao Huan Bei Road, Guangzhou 510005, Guangdong Province, China.

Abstract

Insights

This study reveals how Wnt/β-catenin signaling impacts gene expression in embryonic kidney cells. It identifies key genes and cell types involved in kidney development and immune responses.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genomics

Background:

  • The Wnt/β-catenin signaling pathway is crucial for kidney development.
  • Its precise role in regulating gene expression across different embryonic kidney cell types remains unclear.

Purpose of the Study:

  • To investigate the effects of Wnt/β-catenin signaling activation on gene expression in embryonic mouse kidneys.
  • To identify specific genes and cell types regulated by this pathway during kidney development.

Main Methods:

  • Activated Wnt/β-catenin signaling in E12.5 mouse kidneys in vitro using CHIR99021.
  • Performed RNA sequencing and analyzed differential gene expression (DEGs) in specific kidney cell populations.
  • Utilized single-cell RNA-seq and ChIP-seq data to link DEGs to cell types and identify direct transcriptional targets.

Main Results:

  • Identified 917 significant DEGs upon Wnt/β-catenin activation, including notable up- and down-regulations of specific genes.
  • Single-cell analysis revealed distinct DEG patterns across 19 cell subtypes, with Macrophage_Apoe high cells showing significant enrichment.
  • Found unique gene expression changes in ureteric buds and cap mesenchyme, and identified 221 direct β-catenin targets.

Conclusions:

  • This research maps the complex gene expression landscape regulated by Wnt/β-catenin signaling in embryonic kidney cells.
  • The findings provide insights into the molecular mechanisms of kidney development and the pathway's involvement in immune processes.
  • Establishes a foundation for future studies on Wnt/β-catenin signaling in kidney development and disease.

Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.2K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.3K
Microtubules in Signaling01:22

Microtubules in Signaling

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
1.7K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K