scholarly journals A novel Golgi-associated Vangl2 translational variant required for PCP regulation in vertebrates

2020 ◽  
Author(s):  
Alexandra Walton ◽  
Diego Revinski ◽  
Arnauld Sergé ◽  
Stéphane Audebert ◽  
Luc Camoin ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Developmental Process ◽  
Functional Characterization ◽  
Initiation Site ◽  
Neural Tube Closure ◽  
Start Codon ◽  
Translation Initiation Site ◽  
Tube Closure

AbstractFirst described in Drosophila melanogaster, planar cell polarity (PCP) is a developmental process essential for embryogenesis and development of polarized structures in Metazoans. This signaling pathway involves a set of evolutionarily conserved genes encoding transmembrane (Vangl, Frizzled, Celsr) and cytoplasmic (Prickle, Dishevelled) molecules. Vangl2 is of major importance in embryonic development as illustrated by its pivotal role during neural tube closure in human, mouse, Xenopus and zebrafish embryos. The regulated and poorly understood traffic of Vangl2 to the plasma membrane is a key event for its function in development. Here we report on the molecular and functional characterization of a novel 569-amino acid N-terminally extended Vangl2 isoform, Vangl2-Long, that arises from an alternative non-AUG translation initiation site, lying 144 base pair upstream of the conventional start codon. While missing in Vangl1 paralogs and in all invertebrates, including Drosophila melanogaster, this N-terminal extension is conserved in all vertebrate Vangl2 sequences and confers a subcellular localization in the Golgi apparatus, probably as a result of an extended retention time in this organelle. Vangl2-Long belongs to a multimeric complex with Vangl1 and Vangl2 and we show that its down-regulation leads to severe PCP-related phenotypes in Xenopus embryos, including shorter body axis and neural tube closure defects. Altogether, our study unveils a novel level of complexity in Vangl2 expression, trafficking and function.

scholarly journals Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity

Development ◽  
2013 ◽  
Vol 140 (14) ◽  
pp. 3008-3017 ◽  
Author(s):  
N. Escobedo ◽  
O. Contreras ◽  
R. Munoz ◽  
M. Farias ◽  
H. Carrasco ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Neural Tube Closure ◽  
Tube Closure

scholarly journals Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds

Development ◽  
2021 ◽  
Vol 148 (2) ◽  
pp. dev195008
Author(s):  
Izabela Kowalczyk ◽  
Chanjae Lee ◽  
Elisabeth Schuster ◽  
Josefine Hoeren ◽  
Valentina Trivigno ◽  
...  
Keyword(s):  
Neural Tube ◽  
Planar Cell Polarity ◽  
Adaptor Proteins ◽  
Tube Formation ◽  
Neural Tube Closure ◽  
Model Organisms ◽  
Loss Of Function ◽  
Functional Interaction ◽  
Apical Constriction ◽  
Tube Closure

ABSTRACTPathogenic mutations in the endocytic receptor LRP2 in humans are associated with severe neural tube closure defects (NTDs) such as anencephaly and spina bifida. Here, we have combined analysis of neural tube closure in mouse and in the African Clawed Frog Xenopus laevis to elucidate the etiology of Lrp2-related NTDs. Lrp2 loss of function impaired neuroepithelial morphogenesis, culminating in NTDs that impeded anterior neural plate folding and neural tube closure in both model organisms. Loss of Lrp2 severely affected apical constriction as well as proper localization of the core planar cell polarity (PCP) protein Vangl2, demonstrating a highly conserved role of the receptor in these processes, which are essential for neural tube formation. In addition, we identified a novel functional interaction of Lrp2 with the intracellular adaptor proteins Shroom3 and Gipc1 in the developing forebrain. Our data suggest that, during neurulation, motifs within the intracellular domain of Lrp2 function as a hub that orchestrates endocytic membrane removal for efficient apical constriction, as well as PCP component trafficking in a temporospatial manner.

scholarly journals 03-P026 Retinoic acid – planar cell polarity crosstalk during neural tube closure

2009 ◽  
Vol 126 ◽  
pp. S75
Author(s):  
Ioana Laura Tuduce ◽  
Purushthama Tata Rao ◽  
Xianling Zhao ◽  
Gregg Duester ◽  
Michael Kühl ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Polarity ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Neural Tube Closure ◽  
Tube Closure

scholarly journals Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity

2013 ◽  
Vol 126 (14) ◽  
pp. e1-e1
Author(s):  
N. Escobedo ◽  
O. Contreras ◽  
R. Munoz ◽  
M. Farias ◽  
H. Carrasco ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Neural Tube Closure ◽  
Tube Closure

scholarly journals Severe neural tube defects due to failure of closure initiation can arise without abnormality of neuroepithelial convergent extension

2021 ◽  
Author(s):  
Oleksandr Nychyk ◽  
Gabriel L Galea ◽  
Matteo J Mole ◽  
Dawn Savery ◽  
Nicholas Greene ◽  
...  
Keyword(s):  
Neural Tube ◽  
Planar Cell Polarity ◽  
Gene Mutations ◽  
Initiation Site ◽  
Positive Control ◽  
Severe Form ◽  
Neural Tube Closure ◽  
Null Alleles ◽  
Convergent Extension ◽  
Partial Loss

Planar cell polarity (PCP) signalling is vital for initiation of neural tube closure in mice, with diminished convergent extension (CE) cell movements leading to a severe form of neural tube defect (NTD), termed craniorachischisis (CRN). Some human NTDs are also associated with PCP gene mutations, but affected individuals are generally heterozygous, whereas PCP homozygosity or compound heterozygosity is needed to produce CRN in mice. This suggests human NTDs may involve other genetic or environmental factors, that interact with partial loss of PCP function. We found that reduced sulfation OF glycosaminoglycans (GAGs) interacts with heterozygosity for the Lp allele of Vangl2 (a core PCP gene), to cause CRN in mice. Here, we hypothesised that this GAG-PCP interaction may regulate convergent extension movements, and hence lead to severe NTDs in the context of only partial loss of PCP function. Both Lp and null alleles of Vangl2 gave similar findings. Culture of E8.5 embryos in the presence of chlorate (a GAG sulfation inhibitor), or enzymatic cleavage of GAG chains, led to failure of NT closure initiation in the majority of Lp/+ embryos, whereas few +/+ littermates exhibited CRN. The chlorate effect was rescued by exogenous sulphate. Surprisingly, DiO labeling of the embryonic node demonstrated no abnormality of midline axial extension in chlorate-treated Lp/+ embryos that developed CRN. In contrast, positive control Lp/Lp embryos displayed severe convergent extension defects in this assay. Morphometric analysis of the closure initiation site revealed abnormalities in the size and shape of somites that flank the closing neural tube in chlorate-treated Lp/+ embryos. We conclude that severe NTDs involving failure of closure initiation can arise by a mechanism other than faulty neuroepithelial convergent extension. Matrix-mediated expansion of somites, flanking the closing neural tube, may be required for closure initiation.

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