Rspo1 and Rspo3 are required for sensory lineage neural crest formation in mouse embryos

Dev Dyn. 2024 Apr;253(4):435-446. doi: 10.1002/dvdy.659. Epub 2023 Sep 28.

Abstract

Background: R-spondins (Rspos) are secreted proteins that modulate Wnt/β-catenin signaling. At the early stages of spinal cord development, Wnts (Wnt1, Wnt3a) and Rspos (Rspo1, Rspo3) are co-expressed in the roof plate, suggesting that Rspos are involved in development of dorsal spinal cord and neural crest cells in cooperation with Wnt ligands.

Results: Here, we found that Rspo1 and Rspo3, as well as Wnt1 and Wnt3a, maintained roof-plate-specific expression until late embryonic stages. Rspo1- and Rspo3-double-knock-out (dKO) embryos partially exhibited the phenotype of Wnt1 and Wnt3a dKO embryos. While the number of Ngn2-positive sensory lineage neural crest cells is reduced in Rspo-dKO embryos, development of dorsal spinal cord, including its size and dorso-ventral patterning in early development, elongation of the roof plate, and proliferation of ependymal cells, proceeded normally. Consistent with these slight defects, Wnt/β-catenin signaling was not obviously changed in developing spinal cord of dKO embryos.

Conclusions: Our results show that Rspo1 and Rspo3 are dispensable for most developmental processes involving roof plate-derived Wnt ligands, except for specification of a subtype of neural crest cells. Thus, Rspos may modulate Wnt/β-catenin signaling in a context-dependent manner.

Keywords: R‐spondin; Wnt; morphogenesis; neural crest; roof plate; spinal cord.

Publication types

  • Review

MeSH terms

  • Animals
  • Mice
  • Neural Crest* / metabolism
  • Spinal Cord
  • Wnt Signaling Pathway
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin