Journal Article

DZNE-2020-06048

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transcription factor Runx1 is pro-neurogenic in adult hippocampal precursor cells.

Fukui, H. (First author)DZNE* ; Rünker, A.DZNE* ; Fabel, K.DZNE* ; Buchholz, F. ; Kempermann, G. (Last author)DZNE*

2018
PLOS San Francisco, California, US

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Please use a persistent id in citations: doi:10.1371/journal.pone.0190789

Abstract: Transcription factor Runx1 (Runt Related Transcription Factor 1), plays an important role in the differentiation of hematopoetic stem cells, angiogenesis and the development of nociceptive neurons. These known functions have in common that they relate to lineage decisions. We thus asked whether such role might also be found for Runx1 in adult hippocampal neurogenesis as a process, in which such decisions have to be regulated lifelong. Runx1 shows a widespread low expression in the adult mouse brain, not particularly prominent in the hippocampus and the resident neural precursor cells. Isoforms 1 and 2 of Runx1 (but not 3 to 5) driven by the proximal promoter were expressed in hippocampal precursor cells ex vivo, albeit again at very low levels, and were markedly increased after stimulation with TGF-β1. Under differentiation conditions (withdrawal of growth factors) Runx1 became down-regulated. Overexpression of Runx1 in vitro reduced proliferation, increased survival of precursor cells by reducing apoptosis, and increased neuronal differentiation, while slightly reducing dendritic morphology and complexity. Transfection with dominant-negative Runx1 in hippocampal precursor cells in vitro did not result in differences in neurogenesis. Hippocampal expression of Runx1 correlated with adult neurogenesis (precursor cell proliferation) across BXD recombinant strains of mice and covarying transcripts enriched in the GO categories 'neural precursor cell proliferation' and 'neuron differentiation'. Runx1 is thus a plausible candidate gene to be involved in regulating initial differentiation-related steps of adult neurogenesis. It seems, however, that the relative contribution of Runx1 to such effect is complementary and will explain only small parts of the cell-autonomous pro-differentiation effect.

Keyword(s): Alternative Splicing (MeSH) ; Animals (MeSH) ; Apoptosis: physiology (MeSH) ; Cell Survival: physiology (MeSH) ; Cells, Cultured (MeSH) ; Core Binding Factor Alpha 2 Subunit: genetics (MeSH) ; Core Binding Factor Alpha 2 Subunit: metabolism (MeSH) ; Dendrites: metabolism (MeSH) ; Hippocampus: cytology (MeSH) ; Hippocampus: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Inbred DBA (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Neural Stem Cells: metabolism (MeSH) ; Neurogenesis: physiology (MeSH) ; Protein Isoforms (MeSH) ; RNA, Messenger: metabolism (MeSH) ; Running: physiology (MeSH) ; Species Specificity (MeSH) ; Systems Biology (MeSH) ; Transcriptome (MeSH) ; Transfection (MeSH) ; Transforming Growth Factor beta1: administration & dosage (MeSH) ; Transforming Growth Factor beta1: metabolism (MeSH) ; Volition (MeSH) ; Core Binding Factor Alpha 2 Subunit ; Protein Isoforms ; RNA, Messenger ; Runx1 protein, mouse ; Transforming Growth Factor beta1

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Contributing Institute(s):

1. Adult Neurogenesis (AG Kempermann 1)
2. Dresden Pre 2020 (Dresden Pre 2020)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2018

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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