Balancing WNT signalling in early forebrain development: The role of LRP4 as a modulator of LRP6 function.
LRP4
LRP6
WNT pathway
development
forebrain
genetic modifier
neuroepithelium
neuronal progenitor
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2023
2023
Historique:
received:
24
02
2023
accepted:
28
03
2023
medline:
24
4
2023
pubmed:
24
4
2023
entrez:
24
04
2023
Statut:
epublish
Résumé
The specification of the forebrain relies on the precise regulation of WNT/ß-catenin signalling to support neuronal progenitor cell expansion, patterning, and morphogenesis. Imbalances in WNT signalling activity in the early neuroepithelium lead to congenital disorders, such as neural tube defects (NTDs). LDL receptor-related protein (LRP) family members, including the well-studied receptors LRP5 and LRP6, play critical roles in modulating WNT signalling capacity through tightly regulated interactions with their co-receptor Frizzled, WNT ligands, inhibitors and intracellular WNT pathway components. However, little is known about the function of LRP4 as a potential modulator of WNT signalling in the central nervous system. In this study, we investigated the role of LRP4 in the regulation of WNT signalling during early mouse forebrain development. Our results demonstrate that LRP4 can modulate LRP5- and LRP6-mediated WNT signalling in the developing forebrain prior to the onset of neurogenesis at embryonic stage 9.5 and is therefore essential for accurate neural tube morphogenesis. Specifically, LRP4 functions as a genetic modifier for impaired mitotic activity and forebrain hypoplasia, but not for NTDs in LRP6-deficient mutants.
Identifiants
pubmed: 37091972
doi: 10.3389/fcell.2023.1173688
pii: 1173688
pmc: PMC10119419
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1173688Informations de copyright
Copyright © 2023 Geng, Paul, Kowalczyk, Raimundo, Sporbert, Mamo and Hammes.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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