Regulator of G protein signaling 2 (Rgs2) regulates neural crest development through Pparδ-Sox10 cascade

Sheng Jia Lin, Ming Chang Chiang, Hung Yu Shih, Li Sung Hsu, Tu-Hsueh Yeh, Yin Cheng Huang, Ching-Yu Lin, Yi Chuan Cheng

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Neural crest cells are multipotent progenitors that migrate extensively and differentiate into numerous derivatives. The developmental plasticity and migratory ability of neural crest cells render them an attractive model for studying numerous aspects of cell progression. We observed that zebrafish rgs2 was expressed in neural crest cells. Disrupting Rgs2 expression by using a dominant negative rgs2 construct or rgs2 morpholinos reduced GTPase-activating protein activity, induced the formation of neural crest progenitors, increased the proliferation of nonectomesenchymal neural crest cells, and inhibited the formation of ectomesenchymal neural crest derivatives. The transcription of pparda (which encodes Pparδ, a Wnt-activated transcription factor) was upregulated in Rgs2-deficient embryos, and Pparδ inhibition using a selective antagonist in the Rgs2-deficient embryos repaired neural crest defects. Our results clarify the mechanism through which the Rgs2-Pparδ cascade regulates neural crest development; specifically, Pparδ directly binds to the promoter and upregulates the transcription of the neural crest specifier sox10. This study reveals a unique regulatory mechanism, the Rgs2-Pparδ-Sox10 signaling cascade, and defines a key molecular regulator, Rgs2, in neural crest development.

Original languageEnglish
Pages (from-to)463-474
Number of pages12
JournalBiochimica et Biophysica Acta - General Subjects
Volume1864
Issue number3
DOIs
Publication statusPublished - Mar 2017
Externally publishedYes

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GTP-Binding Protein Regulators
Neural Crest
Transcription
Derivatives
GTPase-Activating Proteins
Morpholinos
Embryonic Structures
Plasticity
Transcription Factors
Zebrafish
Defects
Up-Regulation

Keywords

  • Journal Article

Cite this

Regulator of G protein signaling 2 (Rgs2) regulates neural crest development through Pparδ-Sox10 cascade. / Lin, Sheng Jia; Chiang, Ming Chang; Shih, Hung Yu; Hsu, Li Sung; Yeh, Tu-Hsueh; Huang, Yin Cheng; Lin, Ching-Yu; Cheng, Yi Chuan.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1864, No. 3, 03.2017, p. 463-474.

Research output: Contribution to journalArticle

Lin, Sheng Jia ; Chiang, Ming Chang ; Shih, Hung Yu ; Hsu, Li Sung ; Yeh, Tu-Hsueh ; Huang, Yin Cheng ; Lin, Ching-Yu ; Cheng, Yi Chuan. / Regulator of G protein signaling 2 (Rgs2) regulates neural crest development through Pparδ-Sox10 cascade. In: Biochimica et Biophysica Acta - General Subjects. 2017 ; Vol. 1864, No. 3. pp. 463-474.
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AU - Yeh, Tu-Hsueh

AU - Huang, Yin Cheng

AU - Lin, Ching-Yu

AU - Cheng, Yi Chuan

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N2 - Neural crest cells are multipotent progenitors that migrate extensively and differentiate into numerous derivatives. The developmental plasticity and migratory ability of neural crest cells render them an attractive model for studying numerous aspects of cell progression. We observed that zebrafish rgs2 was expressed in neural crest cells. Disrupting Rgs2 expression by using a dominant negative rgs2 construct or rgs2 morpholinos reduced GTPase-activating protein activity, induced the formation of neural crest progenitors, increased the proliferation of nonectomesenchymal neural crest cells, and inhibited the formation of ectomesenchymal neural crest derivatives. The transcription of pparda (which encodes Pparδ, a Wnt-activated transcription factor) was upregulated in Rgs2-deficient embryos, and Pparδ inhibition using a selective antagonist in the Rgs2-deficient embryos repaired neural crest defects. Our results clarify the mechanism through which the Rgs2-Pparδ cascade regulates neural crest development; specifically, Pparδ directly binds to the promoter and upregulates the transcription of the neural crest specifier sox10. This study reveals a unique regulatory mechanism, the Rgs2-Pparδ-Sox10 signaling cascade, and defines a key molecular regulator, Rgs2, in neural crest development.

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