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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. Key Findings: Rspo1‐ and Rspo3‐double‐knock‐out (dKO) embryos partially exhibited the phenotype of Wnt1 and Wnt3a dKO embryos.The number of Ngn2‐positive sensory lineage neural crest cells is reduced in Rspo‐dKO embryos.Development of dorsal spinal cord proceeded normally in Rspo‐dKO embryos.Wnt/β‐catenin signaling was not obviously changed in developing spinal cord of dKO embryos. [ABSTRACT FROM AUTHOR]

Background/aim: Glioblastoma is the most common and aggressive malignant brain tumor in adults, and glioblastoma stem cells (GSCs) contribute to treatment resistance and recurrence. Inhibition of Stat5b in GSCs suppresses cell proliferation and induces apoptosis. Herein, we investigated the mechanisms of growth inhibition by Stat5b knockdown (KD) in GSCs., Materials and Methods: GSCs were established from a murine glioblastoma model in which shRNA-p53 and EGFR/Ras mutants were induced in vivo using a Sleeping Beauty transposon system. Microarray analyses were performed on Stat5b-KD GSCs to identify genes that are differentially expressed downstream of Stat5b. RT-qPCR and western blot analyses were used to determine Myb levels in GSCs. Myb-overexpressing GSCs were induced by electroporation. Proliferation and apoptosis were evaluated by a trypan blue dye exclusion test and annexin-V staining, respectively., Results: MYB, which is involved in the Wnt pathway, was identified as a novel gene whose expression was down-regulated by Stat5b-KD in GSCs. Both MYB mRNA and protein levels were down-regulated by Stat5b-KD. Overexpression of Myb rescued cell proliferation that was suppressed by Stat5b-KD. Furthermore, Stat5b-KD-induced apoptosis in GSCs was significantly inhibited by Myb overexpression., Conclusion: Down-regulation of Myb mediates Stat5b-KD-induced inhibition of proliferation and induction of apoptosis in GSCs. This may represent a promising novel therapeutic strategy against glioblastoma., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)