FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation

Corinne L. Fairchild, Joseph P. Conway, Andrew T. Schiffmacher, Lisa A. Taneyhill, Laura S Gammill

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The scaffolding protein tetraspanin18 (Tspan18) maintains epithelial cadherin-6B (Cad6B) to antagonize chick cranial neural crest epithelial-to-mesenchymal transition (EMT). For migration to take place, Tspan18 must be downregulated. Here, we characterize the role of the winged-helix transcription factor FoxD3 in the control of Tspan18 expression. Although we previously found that Tspan18 mRNA persists several hours past the stage it would normally be downregulated in FoxD3-deficient neural folds, we now show that Tspan18 expression eventually declines. This indicates that while FoxD3 is crucial for initial downregulation of Tspan18, other factors subsequently impact Tspan18 expression. Remarkably, the classical EMT transcription factor Snail2 is not one of these factors. As in other vertebrates, FoxD3 is required for chick cranial neural crest specification and migration, however, FoxD3 has surprisingly little impact on chick cranial neural crest cell survival. Strikingly, Tspan18 knockdown rescues FoxD3-dependent neural crest migration defects, although neural crest specification is still deficient. This indicates that FoxD3 promotes cranial neural crest EMT by eliciting Tspan18 downregulation separable from its Tspan18-independent activity during neural crest specification and survival.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalMechanisms of Development
Volume132
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Epithelial-Mesenchymal Transition
Neural Crest
Down-Regulation
Winged-Helix Transcription Factors
Cadherins
Vertebrates
Cell Survival
Transcription Factors
Messenger RNA

Keywords

  • EMT
  • FoxD3
  • Migration
  • Neural crest
  • Tetraspanin

Cite this

FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation. / Fairchild, Corinne L.; Conway, Joseph P.; Schiffmacher, Andrew T.; Taneyhill, Lisa A.; Gammill, Laura S.

In: Mechanisms of Development, Vol. 132, No. 1, 01.01.2014, p. 1-12.

Research output: Contribution to journalArticle

Fairchild, Corinne L. ; Conway, Joseph P. ; Schiffmacher, Andrew T. ; Taneyhill, Lisa A. ; Gammill, Laura S. / FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation. In: Mechanisms of Development. 2014 ; Vol. 132, No. 1. pp. 1-12.
@article{e982fc32c29c45bc8053139c69a2ed05,
title = "FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation",
abstract = "The scaffolding protein tetraspanin18 (Tspan18) maintains epithelial cadherin-6B (Cad6B) to antagonize chick cranial neural crest epithelial-to-mesenchymal transition (EMT). For migration to take place, Tspan18 must be downregulated. Here, we characterize the role of the winged-helix transcription factor FoxD3 in the control of Tspan18 expression. Although we previously found that Tspan18 mRNA persists several hours past the stage it would normally be downregulated in FoxD3-deficient neural folds, we now show that Tspan18 expression eventually declines. This indicates that while FoxD3 is crucial for initial downregulation of Tspan18, other factors subsequently impact Tspan18 expression. Remarkably, the classical EMT transcription factor Snail2 is not one of these factors. As in other vertebrates, FoxD3 is required for chick cranial neural crest specification and migration, however, FoxD3 has surprisingly little impact on chick cranial neural crest cell survival. Strikingly, Tspan18 knockdown rescues FoxD3-dependent neural crest migration defects, although neural crest specification is still deficient. This indicates that FoxD3 promotes cranial neural crest EMT by eliciting Tspan18 downregulation separable from its Tspan18-independent activity during neural crest specification and survival.",
keywords = "EMT, FoxD3, Migration, Neural crest, Tetraspanin",
author = "Fairchild, {Corinne L.} and Conway, {Joseph P.} and Schiffmacher, {Andrew T.} and Taneyhill, {Lisa A.} and Gammill, {Laura S}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.mod.2014.02.004",
language = "English (US)",
volume = "132",
pages = "1--12",
journal = "Mechanisms of Development",
issn = "0925-4773",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation

AU - Fairchild, Corinne L.

AU - Conway, Joseph P.

AU - Schiffmacher, Andrew T.

AU - Taneyhill, Lisa A.

AU - Gammill, Laura S

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The scaffolding protein tetraspanin18 (Tspan18) maintains epithelial cadherin-6B (Cad6B) to antagonize chick cranial neural crest epithelial-to-mesenchymal transition (EMT). For migration to take place, Tspan18 must be downregulated. Here, we characterize the role of the winged-helix transcription factor FoxD3 in the control of Tspan18 expression. Although we previously found that Tspan18 mRNA persists several hours past the stage it would normally be downregulated in FoxD3-deficient neural folds, we now show that Tspan18 expression eventually declines. This indicates that while FoxD3 is crucial for initial downregulation of Tspan18, other factors subsequently impact Tspan18 expression. Remarkably, the classical EMT transcription factor Snail2 is not one of these factors. As in other vertebrates, FoxD3 is required for chick cranial neural crest specification and migration, however, FoxD3 has surprisingly little impact on chick cranial neural crest cell survival. Strikingly, Tspan18 knockdown rescues FoxD3-dependent neural crest migration defects, although neural crest specification is still deficient. This indicates that FoxD3 promotes cranial neural crest EMT by eliciting Tspan18 downregulation separable from its Tspan18-independent activity during neural crest specification and survival.

AB - The scaffolding protein tetraspanin18 (Tspan18) maintains epithelial cadherin-6B (Cad6B) to antagonize chick cranial neural crest epithelial-to-mesenchymal transition (EMT). For migration to take place, Tspan18 must be downregulated. Here, we characterize the role of the winged-helix transcription factor FoxD3 in the control of Tspan18 expression. Although we previously found that Tspan18 mRNA persists several hours past the stage it would normally be downregulated in FoxD3-deficient neural folds, we now show that Tspan18 expression eventually declines. This indicates that while FoxD3 is crucial for initial downregulation of Tspan18, other factors subsequently impact Tspan18 expression. Remarkably, the classical EMT transcription factor Snail2 is not one of these factors. As in other vertebrates, FoxD3 is required for chick cranial neural crest specification and migration, however, FoxD3 has surprisingly little impact on chick cranial neural crest cell survival. Strikingly, Tspan18 knockdown rescues FoxD3-dependent neural crest migration defects, although neural crest specification is still deficient. This indicates that FoxD3 promotes cranial neural crest EMT by eliciting Tspan18 downregulation separable from its Tspan18-independent activity during neural crest specification and survival.

KW - EMT

KW - FoxD3

KW - Migration

KW - Neural crest

KW - Tetraspanin

UR - http://www.scopus.com/inward/record.url?scp=84897028054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897028054&partnerID=8YFLogxK

U2 - 10.1016/j.mod.2014.02.004

DO - 10.1016/j.mod.2014.02.004

M3 - Article

C2 - 24582980

AN - SCOPUS:84897028054

VL - 132

SP - 1

EP - 12

JO - Mechanisms of Development

JF - Mechanisms of Development

SN - 0925-4773

IS - 1

ER -