Deltex1 is inhibited by the Notch-Hairy/E(Spl) signaling pathway and induces neuronal and glial differentiation

Yi Chuan Cheng, Yin Cheng Huang, Tu Hsueh Yeh, Hung Yu Shih, Ching Yu Lin, Sheng Jia Lin, Ching Chi Chiu, Wen Ching Huang, Yun Jin Jiang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Notch signaling has been conserved throughout evolution and plays a fundamental role in various neural developmental processes and the pathogenesis of several human cancers and genetic disorders. However, how Notch signaling regulates various cellular processes remains unclear. Although Deltex proteins have been identified as cytoplasmic downstream elements of the Notch signaling pathway, few studies have been reported on their physiological role. Results: We isolated zebrafish deltex1 (dtx1) and showed that this gene is primarily transcribed in the developing nervous system, and its spatiotemporal expression pattern suggests a role in neural differentiation. The transcription of dtx1 was suppressed by the direct binding of the Notch downstream transcription factors Her2 and Her8a. Overexpressing the complete coding sequence of Dtx1 was necessary for inducing neuronal and glial differentiation. By contrast, disrupting Dtx1 expression by using a Dtx1 construct without the RING finger domain reduced neuronal and glial differentiation. This effect was phenocopied by the knockdown of endogenous Dtx1 expression by using morpholinos, demonstrating the essential function of the RING finger domain and confirming the knockdown specificity. Cell proliferation and apoptosis were unaltered in Dtx1-overexpressed and -deficient zebrafish embryos. Examination of the expression of her2 and her8a in embryos with altered Dtx1 expression showed that Dxt1-induced neuronal differentiation did not require a regulatory effect on the Notch-Hairy/E(Spl) pathway. However, both Dtx1 and Notch activation induced glial differentiation, and Dtx1 and Notch activation negatively inhibited each other in a reciprocal manner, which achieves a proper balance for the expression of Dtx1 and Notch to facilitate glial differentiation. We further confirmed that the Dtx1-Notch-Hairy/E(Spl) cascade was sufficient to induce neuronal and glial differentiation by concomitant injection of an active form of Notch with dtx1, which rescued the neuronogenic and gliogenic defects caused by the activation of Notch signaling. Conclusions: Our results demonstrated that Dtx1 is regulated by Notch-Hairy/E(Spl) signaling and is a major factor specifically regulating neural differentiation. Thus, our results provide new insights into the mediation of neural development by the Notch signaling pathway.

Original languageEnglish
Article number28
JournalNeural Development
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 30 2015
Externally publishedYes

Fingerprint

Neuroglia
RING Finger Domains
Zebrafish
Embryonic Structures
Morpholinos
Inborn Genetic Diseases
Medical Genetics
Nervous System
Transcription Factors
Cell Proliferation
Apoptosis
Injections
Genes
Neoplasms
Proteins

Keywords

  • Dtx1
  • Hairy/E(Spl)
  • Neural differentiation
  • Notch
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Neuroscience

Cite this

Deltex1 is inhibited by the Notch-Hairy/E(Spl) signaling pathway and induces neuronal and glial differentiation. / Cheng, Yi Chuan; Huang, Yin Cheng; Yeh, Tu Hsueh; Shih, Hung Yu; Lin, Ching Yu; Lin, Sheng Jia; Chiu, Ching Chi; Huang, Wen Ching; Jiang, Yun Jin.

In: Neural Development, Vol. 10, No. 1, 28, 30.12.2015.

Research output: Contribution to journalArticle

Cheng, Yi Chuan ; Huang, Yin Cheng ; Yeh, Tu Hsueh ; Shih, Hung Yu ; Lin, Ching Yu ; Lin, Sheng Jia ; Chiu, Ching Chi ; Huang, Wen Ching ; Jiang, Yun Jin. / Deltex1 is inhibited by the Notch-Hairy/E(Spl) signaling pathway and induces neuronal and glial differentiation. In: Neural Development. 2015 ; Vol. 10, No. 1.
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AU - Shih, Hung Yu

AU - Lin, Ching Yu

AU - Lin, Sheng Jia

AU - Chiu, Ching Chi

AU - Huang, Wen Ching

AU - Jiang, Yun Jin

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