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Genetic requirement of to regulate noncanonical Wnt signaling and during embryonic convergent extension and craniofacial morphogenesis.

作者信息

Carroll Shannon H, Schafer Sogand, Kawasaki Kenta, Tsimbal Casey, Julé Amélie M, Hallett Shawn A, Li Edward, Liao Eric C

机构信息

Center for Craniofacial Innovation, Children's Hospital of Philadelphia Research Institute, Children's Hospital of Philadelphia, PA 19104, USA.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Children's Hospital of Philadelphia, PA 19104, USA.

出版信息

bioRxiv. 2024 Sep 4:2023.11.07.566024. doi: 10.1101/2023.11.07.566024.


DOI:10.1101/2023.11.07.566024
PMID:37986847
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10659360/
Abstract

Wnt signaling plays crucial roles in embryonic patterning including the regulation of convergent extension during gastrulation, the establishment of the dorsal axis, and later, craniofacial morphogenesis. Further, Wnt signaling is a crucial regulator of craniofacial morphogenesis. The adapter proteins Dact1 and Dact2 modulate the Wnt signaling pathway through binding to Disheveled. However, the distinct relative functions of Dact1 and Dact2 during embryogenesis remain unclear. We found that and genes have dynamic spatiotemporal expression domains that are reciprocal to one another suggesting distinct functions during zebrafish embryogenesis. Both and contribute to axis extension, with compound mutants exhibiting a similar convergent extension defect and craniofacial phenotype to the mutant. Utilizing single-cell RNAseq and an established noncanonical Wnt pathway mutant with a shortened axis (), we identified specific roles during early development. Comparative whole transcriptome analysis between wildtype and and wildtype and compound mutants revealed a novel role for in regulating the mRNA expression of the classical calpain . Over-expression of phenocopies craniofacial dysmorphology. These results identify a previously unappreciated role of and calcium-dependent proteolysis during embryogenesis. Taken together, our findings highlight the distinct and overlapping roles of and in embryonic craniofacial development, providing new insights into the multifaceted regulation of Wnt signaling.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/0f91ba5ee393/nihpp-2023.11.07.566024v3-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/0a79aed1efe7/nihpp-2023.11.07.566024v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/8ade9f695f09/nihpp-2023.11.07.566024v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/0844e6316fc3/nihpp-2023.11.07.566024v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/cff5112155da/nihpp-2023.11.07.566024v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/8cbddca4674b/nihpp-2023.11.07.566024v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/221c3779ffa6/nihpp-2023.11.07.566024v3-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/d6d860ee085a/nihpp-2023.11.07.566024v3-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/0f91ba5ee393/nihpp-2023.11.07.566024v3-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/0a79aed1efe7/nihpp-2023.11.07.566024v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/8ade9f695f09/nihpp-2023.11.07.566024v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/0844e6316fc3/nihpp-2023.11.07.566024v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/cff5112155da/nihpp-2023.11.07.566024v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/8cbddca4674b/nihpp-2023.11.07.566024v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/221c3779ffa6/nihpp-2023.11.07.566024v3-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/d6d860ee085a/nihpp-2023.11.07.566024v3-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/11422982/0f91ba5ee393/nihpp-2023.11.07.566024v3-f0008.jpg

相似文献

[1]
Genetic requirement of to regulate noncanonical Wnt signaling and during embryonic convergent extension and craniofacial morphogenesis.

bioRxiv. 2024-9-4

[2]
Genetic requirement of to regulate noncanonical Wnt signaling and during embryonic convergent extension and craniofacial morphogenesis.

Elife. 2024-11-21

[3]
SEC14 and spectrin domains 1 (Sestd1) and Dapper antagonist of catenin 1 (Dact1) scaffold proteins cooperatively regulate the Van Gogh-like 2 (Vangl2) four-pass transmembrane protein and planar cell polarity (PCP) pathway during embryonic development in mice.

J Biol Chem. 2013-5-21

[4]
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Nucleosides Nucleotides Nucleic Acids. 2024

[5]
Dact1-3 mRNAs exhibit distinct expression domains during tooth development.

Gene Expr Patterns. 2010

[6]
Identification and characterization of rat Dact1 and Dact2 genes in silico.

Int J Mol Med. 2005-6

[7]
Dact gene expression profiles suggest a role for this gene family in integrating Wnt and TGF-β signaling pathways during chicken limb development.

Dev Dyn. 2014-3

[8]
Roles of Wnt pathway genes wls, wnt9a, wnt5b, frzb and gpc4 in regulating convergent-extension during zebrafish palate morphogenesis.

Development. 2016-7-15

[9]
Dact2 represses PITX2 transcriptional activation and cell proliferation through Wnt/beta-catenin signaling during odontogenesis.

PLoS One. 2013-1-22

[10]
Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma.

J Biomed Sci. 2017-1-11

本文引用的文献

[1]
Calpain 8 as a potential biomarker regulates the progression of pancreatic cancer via EMT and AKT/ERK pathway.

J Proteomics. 2024-6-15

[2]
CAPN8 involves with exhausted, inflamed, and desert immune microenvironment to influence the metastasis of thyroid cancer.

Front Immunol. 2022

[3]
Wnt/planar cell polarity signaling controls morphogenetic movements of gastrulation and neural tube closure.

Cell Mol Life Sci. 2022-11-12

[4]
Zebrafish information network, the knowledgebase for Danio rerio research.

Genetics. 2022-4-4

[5]
clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.

Innovation (Camb). 2021-7-1

[6]
The Emerging Mechanisms of Wnt Secretion and Signaling in Development.

Front Cell Dev Biol. 2021-8-16

[7]
Integrated analysis of multimodal single-cell data.

Cell. 2021-6-24

[8]
Synergistic roles of Wnt modulators R-spondin2 and R-spondin3 in craniofacial morphogenesis and dental development.

Sci Rep. 2021-3-12

[9]
An - regulatory axis controls midface morphogenesis in vertebrates.

Development. 2020-12-23

[10]
WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders.

Front Endocrinol (Lausanne). 2020

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