Transcriptomic profile of Pea3 family members reveal regulatory codes for axon outgrowth and neuronal connection specificity.

Abstract:

:PEA3 transcription factor subfamily is present in a variety of tissues with branching morphogenesis, and play a particularly significant role in neural circuit formation and specificity. Many target genes in axon guidance and cell-cell adhesion pathways have been identified for Pea3 transcription factor (but not for Erm or Er81); however it was not so far clear whether all Pea3 subfamily members regulate same target genes, or whether there are unique targets for each subfamily member that help explain the exclusivity and specificity of these proteins in neuronal circuit formation. In this study, using transcriptomics and qPCR analyses in SH-SY5Y neuroblastoma cells, hypothalamic and hippocampal cell line, we have identified cell type-specific and subfamily member-specific targets for PEA3 transcription factor subfamily. While Pea3 upregulates transcription of Sema3D and represses Sema5B, for example, Erm and Er81 upregulate Sema5A and Er81 regulates Unc5C and Sema4G while repressing EFNB3 in SH-SY5Y neuroblastoma cells. We furthermore present a molecular model of how unique sites within the ETS domain of each family member can help recognize specific target motifs. Such cell-context and member-specific combinatorial expression profiles help identify cell-cell and cell-extracellular matrix communication networks and how they establish specific connections.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Kandemir B,Gulfidan G,Arga KY,Yilmaz B,Kurnaz IA

doi

10.1038/s41598-020-75089-3

subject

Has Abstract

pub_date

2020-10-23 00:00:00

pages

18162

issue

1

issn

2045-2322

pii

10.1038/s41598-020-75089-3

journal_volume

10

pub_type

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