Evolution of the chordate regeneration blastema: Differential gene expression and conserved role of notch signaling during siphon regeneration in the ascidian Ciona

Mayuko Hamada, Spela Goricki, Mardi S. Byerly, Noriyuki Satoh, William R. Jeffery

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The regeneration of the oral siphon (OS) and other distal structures in the ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a blastema of proliferating cells. Despite the longstanding use of Ciona as a model in molecular developmental biology, regeneration in this system has not been previously explored by molecular analysis. Here we have employed microarray analysis and quantitative real time RT-PCR to identify genes with differential expression profiles during OS regeneration. The majority of differentially expressed genes were downregulated during OS regeneration, suggesting roles in normal growth and homeostasis. However, a subset of differentially expressed genes was upregulated in the regenerating OS, suggesting functional roles during regeneration. Among the upregulated genes were key members of the Notch signaling pathway, including those encoding the delta and jagged ligands, two fringe modulators, and to a lesser extent the notch receptor. In situ hybridization showed a complementary pattern of delta1 and notch gene expression in the blastema of the regenerating OS. Chemical inhibition of the Notch signaling pathway reduced the levels of cell proliferation in the branchial sac, a stem cell niche that contributes progenitor cells to the regenerating OS, and in the OS regeneration blastema, where siphon muscle fibers eventually re-differentiate. Chemical inhibition also prevented the replacement of oral siphon pigment organs, sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but had no effects on the formation of the wound epidermis. Since Notch signaling is involved in the maintenance of proliferative activity in both the Ciona and vertebrate regeneration blastema, the results suggest a conserved evolutionary role of this signaling pathway in chordate regeneration. The genes identified in this investigation provide the foundation for future molecular analysis of OS regeneration.

Original languageEnglish
Pages (from-to)304-315
Number of pages12
JournalDevelopmental Biology
Volume405
Issue number2
DOIs
Publication statusPublished - Sep 15 2015
Externally publishedYes

Fingerprint

Chordata
Urochordata
Regeneration
Gene Expression
Genes
Ciona intestinalis
Notch Receptors
Stem Cell Niche
Developmental Biology
Muscles
Sensory Receptor Cells
Microarray Analysis
Epidermis
In Situ Hybridization
Vertebrates
Real-Time Polymerase Chain Reaction
Molecular Biology
Homeostasis
Stem Cells
Down-Regulation

Keywords

  • Blastema
  • Cell
  • Ciona intestinalis
  • Differential gene expression
  • Muscle differentiation
  • Notch pathway
  • Proliferation
  • Regeneration

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Evolution of the chordate regeneration blastema : Differential gene expression and conserved role of notch signaling during siphon regeneration in the ascidian Ciona. / Hamada, Mayuko; Goricki, Spela; Byerly, Mardi S.; Satoh, Noriyuki; Jeffery, William R.

In: Developmental Biology, Vol. 405, No. 2, 15.09.2015, p. 304-315.

Research output: Contribution to journalArticle

@article{ffef96cce0a74372b042b136a84efff2,
title = "Evolution of the chordate regeneration blastema: Differential gene expression and conserved role of notch signaling during siphon regeneration in the ascidian Ciona",
abstract = "The regeneration of the oral siphon (OS) and other distal structures in the ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a blastema of proliferating cells. Despite the longstanding use of Ciona as a model in molecular developmental biology, regeneration in this system has not been previously explored by molecular analysis. Here we have employed microarray analysis and quantitative real time RT-PCR to identify genes with differential expression profiles during OS regeneration. The majority of differentially expressed genes were downregulated during OS regeneration, suggesting roles in normal growth and homeostasis. However, a subset of differentially expressed genes was upregulated in the regenerating OS, suggesting functional roles during regeneration. Among the upregulated genes were key members of the Notch signaling pathway, including those encoding the delta and jagged ligands, two fringe modulators, and to a lesser extent the notch receptor. In situ hybridization showed a complementary pattern of delta1 and notch gene expression in the blastema of the regenerating OS. Chemical inhibition of the Notch signaling pathway reduced the levels of cell proliferation in the branchial sac, a stem cell niche that contributes progenitor cells to the regenerating OS, and in the OS regeneration blastema, where siphon muscle fibers eventually re-differentiate. Chemical inhibition also prevented the replacement of oral siphon pigment organs, sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but had no effects on the formation of the wound epidermis. Since Notch signaling is involved in the maintenance of proliferative activity in both the Ciona and vertebrate regeneration blastema, the results suggest a conserved evolutionary role of this signaling pathway in chordate regeneration. The genes identified in this investigation provide the foundation for future molecular analysis of OS regeneration.",
keywords = "Blastema, Cell, Ciona intestinalis, Differential gene expression, Muscle differentiation, Notch pathway, Proliferation, Regeneration",
author = "Mayuko Hamada and Spela Goricki and Byerly, {Mardi S.} and Noriyuki Satoh and Jeffery, {William R.}",
year = "2015",
month = "9",
day = "15",
doi = "10.1016/j.ydbio.2015.07.017",
language = "English",
volume = "405",
pages = "304--315",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Evolution of the chordate regeneration blastema

T2 - Differential gene expression and conserved role of notch signaling during siphon regeneration in the ascidian Ciona

AU - Hamada, Mayuko

AU - Goricki, Spela

AU - Byerly, Mardi S.

AU - Satoh, Noriyuki

AU - Jeffery, William R.

PY - 2015/9/15

Y1 - 2015/9/15

N2 - The regeneration of the oral siphon (OS) and other distal structures in the ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a blastema of proliferating cells. Despite the longstanding use of Ciona as a model in molecular developmental biology, regeneration in this system has not been previously explored by molecular analysis. Here we have employed microarray analysis and quantitative real time RT-PCR to identify genes with differential expression profiles during OS regeneration. The majority of differentially expressed genes were downregulated during OS regeneration, suggesting roles in normal growth and homeostasis. However, a subset of differentially expressed genes was upregulated in the regenerating OS, suggesting functional roles during regeneration. Among the upregulated genes were key members of the Notch signaling pathway, including those encoding the delta and jagged ligands, two fringe modulators, and to a lesser extent the notch receptor. In situ hybridization showed a complementary pattern of delta1 and notch gene expression in the blastema of the regenerating OS. Chemical inhibition of the Notch signaling pathway reduced the levels of cell proliferation in the branchial sac, a stem cell niche that contributes progenitor cells to the regenerating OS, and in the OS regeneration blastema, where siphon muscle fibers eventually re-differentiate. Chemical inhibition also prevented the replacement of oral siphon pigment organs, sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but had no effects on the formation of the wound epidermis. Since Notch signaling is involved in the maintenance of proliferative activity in both the Ciona and vertebrate regeneration blastema, the results suggest a conserved evolutionary role of this signaling pathway in chordate regeneration. The genes identified in this investigation provide the foundation for future molecular analysis of OS regeneration.

AB - The regeneration of the oral siphon (OS) and other distal structures in the ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a blastema of proliferating cells. Despite the longstanding use of Ciona as a model in molecular developmental biology, regeneration in this system has not been previously explored by molecular analysis. Here we have employed microarray analysis and quantitative real time RT-PCR to identify genes with differential expression profiles during OS regeneration. The majority of differentially expressed genes were downregulated during OS regeneration, suggesting roles in normal growth and homeostasis. However, a subset of differentially expressed genes was upregulated in the regenerating OS, suggesting functional roles during regeneration. Among the upregulated genes were key members of the Notch signaling pathway, including those encoding the delta and jagged ligands, two fringe modulators, and to a lesser extent the notch receptor. In situ hybridization showed a complementary pattern of delta1 and notch gene expression in the blastema of the regenerating OS. Chemical inhibition of the Notch signaling pathway reduced the levels of cell proliferation in the branchial sac, a stem cell niche that contributes progenitor cells to the regenerating OS, and in the OS regeneration blastema, where siphon muscle fibers eventually re-differentiate. Chemical inhibition also prevented the replacement of oral siphon pigment organs, sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but had no effects on the formation of the wound epidermis. Since Notch signaling is involved in the maintenance of proliferative activity in both the Ciona and vertebrate regeneration blastema, the results suggest a conserved evolutionary role of this signaling pathway in chordate regeneration. The genes identified in this investigation provide the foundation for future molecular analysis of OS regeneration.

KW - Blastema

KW - Cell

KW - Ciona intestinalis

KW - Differential gene expression

KW - Muscle differentiation

KW - Notch pathway

KW - Proliferation

KW - Regeneration

UR - http://www.scopus.com/inward/record.url?scp=84939270049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939270049&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2015.07.017

DO - 10.1016/j.ydbio.2015.07.017

M3 - Article

C2 - 26206613

AN - SCOPUS:84939270049

VL - 405

SP - 304

EP - 315

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -