Snx3 is important for mammalian neural tube closure via its role in canonical and non-canonical WNT signaling.

Development
Heather Mary BrownLee A Niswander

Abstract

Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3-/- mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3-/- embryos and a defect in convergent extension of the neural epithelium. Snx3-/- cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance of SNX3 in WNT signaling regulation is demonstrated by rescue of NT closure in Snx3-/- embryos with a WNT agonist. The potential for SNX3 to function in human neurulation is revealed by a point mutation identified in an NTD-affected individual that results in functionally impaired SNX3 that does not colocalize with WLS and the degradation of WLS in the lysosome. These data indicate that Snx3 is crucial for NT closure via its role in recycling WLS in order to control levels of WNT signaling.

References

Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·P S Klein, D A Melton
Oct 23, 2001·Developmental Dynamics : an Official Publication of the American Association of Anatomists·G Holmes, L Niswander
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·Carolyn A Worby, Jack E Dixon
Sep 30, 2003·The Journal of Biological Chemistry·Cong-Zhao ZhouHerman van Tilbeurgh
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Catriona Y Logan, Roel Nusse
Aug 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Michelle CarterM Elizabeth Ross
Nov 17, 2006·Development·Robyn M GoodmanErica M Selva
Dec 21, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Muriel J Harris, Diana M Juriloff
Apr 17, 2007·Developmental Biology·Dong QianPing Chen
Dec 20, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Trisha Castranio, Yuji Mishina
Aug 25, 2009·Development·Lanying SongChengji J Zhou
Apr 27, 2010·Developmental Disabilities Research Reviews·Kit Sing AuHope Northrup
Jun 15, 2010·Birth Defects Research. Part A, Clinical and Molecular Teratology·Jennifer N Murdoch, Andrew J Copp
Jan 20, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jiang FuWei Hsu
Jul 5, 2011·Nature Cell Biology·Ludger Johannes, Christian Wunder
Apr 19, 2012·Development·Heather J Ray, Lee Niswander
Oct 2, 2012·Birth Defects Research. Part A, Clinical and Molecular Teratology·Diana M Juriloff, Muriel J Harris
Nov 13, 2012·Current Topics in Developmental Biology·Bo Gao
Nov 22, 2012·Nature Communications·Caleb S HeffnerStephen A Murray
Feb 19, 2013·Cell Metabolism·Caiyong ChenBarry H Paw
Apr 29, 2014·Developmental Cell·Jia YuDavid M Virshup
Sep 10, 2014·Birth Defects Research. Part A, Clinical and Molecular Teratology·Redouane AllacheZoha Kibar
Oct 9, 2014·Annual Review of Genetics·Jonathan J WildeLee Niswander
Nov 29, 2014·Current Protocols in Bioinformatics·Geraldine A Van der AuweraMark A DePristo
Nov 28, 2016·Cell·María LucasAitor Hierro
Dec 23, 2016·Birth Defects Research·Bethany A StokesIrene E Zohn
Apr 19, 2018·Traffic·Jing WangDaniel D Billadeau
Aug 24, 2018·Journal of Developmental Biology·Diana M Juriloff, Muriel J Harris

❮ Previous
Next ❯

Citations

Dec 17, 2020·Frontiers in Cell and Developmental Biology·Binbin Li, Lee A Niswander
May 2, 2021·Molecular Neurobiology·Neide VieiraNuno Sousa

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.