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Grabylnikov, I.

Publications and source records attributed to Grabylnikov, I..

2 recordsLinked to original sources

The lipid raft-linker gene Raftlin-2 is expressed in migrating neural crest cells

Transient plasma membrane domains called lipid rafts have emerged as important regulators of signal transduction. These territories are formed by lipid-lipid and lipid-protein interactions, and these local interactions can be scaffolded by resident lipid raft organizing protein family members. While roles for lipid rafts have been described for multiple signaling pathways in many contexts, their in vivo prevalence and role during embryonic development remains incompletely understood. Here we examined gene expression for the Raftlin family of lipid raft organizing proteins, Raftlin (RFTN1) and Raftlin-2 (RFTN2), over the course of early vertebrate development, with a focus on neural crest cell dynamics. By analyzing transcriptomic data across vertebrate species, we identified conserved patterns of RFTN1 and RFTN2 expression across species, where RFTN1 is broadly expressed at low levels, while RFTN2 is distinctly enriched in neural crest cells. We used fluorescent in situ hybridization to spatially define Raftlin gene expression patterns in the early avian embryo. Our results show that RFTN1 is broadly expressed with periods of enrichment in the developing paraxial mesoderm. In contrast, RFTN2 expression is strongly enriched in neural crest cells, beginning during specification and persisting through migration, with additional expression in both the cranial and intermediate mesoderm. Together, these patterns suggest that Raftlins may play important roles in regulating signaling during development with specific roles in somitogenesis and in neural crest and mesodermal cell migrations.

Developmental Biology↗

Sphingolipid metabolism is spatially regulated in the developing embryo by SOXE genes

During epithelial-to-mesenchymal transition (EMT), significant rearrangements occur in plasma membrane protein and lipid content that are important for membrane function and acquisition of cell motility. To gain insight into how neural crest cells regulate their lipid content at the transcriptional level during EMT, here we identify critical enhancer sequences that regulate the expression of SMPD3, a gene responsible for sphingomyelin hydrolysis to produce ceramide, which is necessary for neural crest EMT. We uncovered three enhancer regions within the first intron of the SMPD3 locus that drive reporter expression in distinct spatial and temporal domains, together collectively recapitulating the expression domains of endogenous SMPD3 within the ectodermal lineages. We further dissected one enhancer that is specifically active in the migrating neural crest. By mutating putative transcriptional input sites or knocking down upstream regulators, we find that the SoxE-family transcription factors Sox9 and Sox10 regulate the expression of SMPD3 in migrating neural crest cells. Together these results shed light on how core components of developmental gene regulatory networks interact with metabolic effector genes to control changes in membrane lipid content. HighlightsO_LISMPD3 is expressed in the neural tube, neural crest, and notochord during early development C_LIO_LISMPD3 expression is regulated by at least three intronic enhancers C_LIO_LISox10 and its binding sites are required for expression by a migratory neural crest-specific SMPD3 enhancer C_LIO_LISox10 is a positive regulator of endogenous SMPD3 expression during neural crest migration C_LI

developmental biology↗