Combinatorial roles for BMPs and endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton

Courtney Alexander, Elizabeth Zuniga, Ira L. Blitz, Naoyuki Wada, Pierre le Pabic, Yashar Javidan, Tailin Zhang, Ken W. Cho, J. Gage Crump, Thomas F. Schilling

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

SUMMARY Bone morphogenetic proteins (BMPs) play crucial roles in craniofacial development but little is known about their interactions with other signals, such as Endothelin 1 (Edn1) and Jagged/Notch, which pattern the dorsal-ventral (DV) axis of the pharyngeal arches. Here, we use transgenic zebrafish to monitor and perturb BMP signaling during arch formation. With a BMP-responsive transgene, Tg(Bre:GFP), we show active BMP signaling in neural crest (NC)-derived skeletal precursors of the ventral arches, and in surrounding epithelia. Loss-of-function studies using a heat shock-inducible, dominant-negative BMP receptor 1a [Tg(hs70I:dnBmpr1a-GFP)] to bypass early roles show that BMP signaling is required for ventral arch development just after NC migration, the same stages at which we detect Tg(Bre:GFP). Inhibition of BMP signaling at these stages reduces expression of the ventral signal Edn1, as well as ventral-specific genes such as hand2 and dlx6a in the arches, and expands expression of the dorsal signal jag1b. This results in a loss or reduction of ventral and intermediate skeletal elements and a mis-shapen dorsal arch skeleton. Conversely, ectopic BMP causes dorsal expansion of ventral-specific gene expression and corresponding reductions/transformations of dorsal cartilages. Soon after NC migration, BMP is required to induce Edn1 and overexpression of either signal partially rescues ventral skeletal defects in embryos deficient for the other. However, once arch primordia are established the effects of BMPs become restricted to more ventral and anterior (palate) domains, which do not depend on Edn1. This suggests that BMPs act upstream and in parallel to Edn1 to promote ventral fates in the arches during early DV patterning, but later acquire distinct roles that further subdivide the identities of NC cells to pattern the craniofacial skeleton.

Original languageEnglish (US)
Pages (from-to)5135-5146
Number of pages12
JournalDevelopment
Volume138
Issue number23
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 1
Bone Morphogenetic Proteins
Endothelin-1
Skeleton
Neural Crest
Bone Morphogenetic Protein Receptors
Branchial Region
Palate
Zebrafish
Transgenes
Cartilage
Shock

Keywords

  • Branchial arch
  • Craniofacial
  • Neural crest
  • Pharyngeal arch
  • Xenopus
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Alexander, C., Zuniga, E., Blitz, I. L., Wada, N., le Pabic, P., Javidan, Y., ... Schilling, T. F. (2011). Combinatorial roles for BMPs and endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton. Development, 138(23), 5135-5146. https://doi.org/10.1242/dev.067801

Combinatorial roles for BMPs and endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton. / Alexander, Courtney; Zuniga, Elizabeth; Blitz, Ira L.; Wada, Naoyuki; le Pabic, Pierre; Javidan, Yashar; Zhang, Tailin; Cho, Ken W.; Crump, J. Gage; Schilling, Thomas F.

In: Development, Vol. 138, No. 23, 01.12.2011, p. 5135-5146.

Research output: Contribution to journalArticle

Alexander, C, Zuniga, E, Blitz, IL, Wada, N, le Pabic, P, Javidan, Y, Zhang, T, Cho, KW, Crump, JG & Schilling, TF 2011, 'Combinatorial roles for BMPs and endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton', Development, vol. 138, no. 23, pp. 5135-5146. https://doi.org/10.1242/dev.067801
Alexander, Courtney ; Zuniga, Elizabeth ; Blitz, Ira L. ; Wada, Naoyuki ; le Pabic, Pierre ; Javidan, Yashar ; Zhang, Tailin ; Cho, Ken W. ; Crump, J. Gage ; Schilling, Thomas F. / Combinatorial roles for BMPs and endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton. In: Development. 2011 ; Vol. 138, No. 23. pp. 5135-5146.
@article{ea930c5f7f2e416f84cad8b278edc47f,
title = "Combinatorial roles for BMPs and endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton",
abstract = "SUMMARY Bone morphogenetic proteins (BMPs) play crucial roles in craniofacial development but little is known about their interactions with other signals, such as Endothelin 1 (Edn1) and Jagged/Notch, which pattern the dorsal-ventral (DV) axis of the pharyngeal arches. Here, we use transgenic zebrafish to monitor and perturb BMP signaling during arch formation. With a BMP-responsive transgene, Tg(Bre:GFP), we show active BMP signaling in neural crest (NC)-derived skeletal precursors of the ventral arches, and in surrounding epithelia. Loss-of-function studies using a heat shock-inducible, dominant-negative BMP receptor 1a [Tg(hs70I:dnBmpr1a-GFP)] to bypass early roles show that BMP signaling is required for ventral arch development just after NC migration, the same stages at which we detect Tg(Bre:GFP). Inhibition of BMP signaling at these stages reduces expression of the ventral signal Edn1, as well as ventral-specific genes such as hand2 and dlx6a in the arches, and expands expression of the dorsal signal jag1b. This results in a loss or reduction of ventral and intermediate skeletal elements and a mis-shapen dorsal arch skeleton. Conversely, ectopic BMP causes dorsal expansion of ventral-specific gene expression and corresponding reductions/transformations of dorsal cartilages. Soon after NC migration, BMP is required to induce Edn1 and overexpression of either signal partially rescues ventral skeletal defects in embryos deficient for the other. However, once arch primordia are established the effects of BMPs become restricted to more ventral and anterior (palate) domains, which do not depend on Edn1. This suggests that BMPs act upstream and in parallel to Edn1 to promote ventral fates in the arches during early DV patterning, but later acquire distinct roles that further subdivide the identities of NC cells to pattern the craniofacial skeleton.",
keywords = "Branchial arch, Craniofacial, Neural crest, Pharyngeal arch, Xenopus, Zebrafish",
author = "Courtney Alexander and Elizabeth Zuniga and Blitz, {Ira L.} and Naoyuki Wada and {le Pabic}, Pierre and Yashar Javidan and Tailin Zhang and Cho, {Ken W.} and Crump, {J. Gage} and Schilling, {Thomas F.}",
year = "2011",
month = "12",
day = "1",
doi = "10.1242/dev.067801",
language = "English (US)",
volume = "138",
pages = "5135--5146",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "23",

}

TY - JOUR

T1 - Combinatorial roles for BMPs and endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton

AU - Alexander, Courtney

AU - Zuniga, Elizabeth

AU - Blitz, Ira L.

AU - Wada, Naoyuki

AU - le Pabic, Pierre

AU - Javidan, Yashar

AU - Zhang, Tailin

AU - Cho, Ken W.

AU - Crump, J. Gage

AU - Schilling, Thomas F.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - SUMMARY Bone morphogenetic proteins (BMPs) play crucial roles in craniofacial development but little is known about their interactions with other signals, such as Endothelin 1 (Edn1) and Jagged/Notch, which pattern the dorsal-ventral (DV) axis of the pharyngeal arches. Here, we use transgenic zebrafish to monitor and perturb BMP signaling during arch formation. With a BMP-responsive transgene, Tg(Bre:GFP), we show active BMP signaling in neural crest (NC)-derived skeletal precursors of the ventral arches, and in surrounding epithelia. Loss-of-function studies using a heat shock-inducible, dominant-negative BMP receptor 1a [Tg(hs70I:dnBmpr1a-GFP)] to bypass early roles show that BMP signaling is required for ventral arch development just after NC migration, the same stages at which we detect Tg(Bre:GFP). Inhibition of BMP signaling at these stages reduces expression of the ventral signal Edn1, as well as ventral-specific genes such as hand2 and dlx6a in the arches, and expands expression of the dorsal signal jag1b. This results in a loss or reduction of ventral and intermediate skeletal elements and a mis-shapen dorsal arch skeleton. Conversely, ectopic BMP causes dorsal expansion of ventral-specific gene expression and corresponding reductions/transformations of dorsal cartilages. Soon after NC migration, BMP is required to induce Edn1 and overexpression of either signal partially rescues ventral skeletal defects in embryos deficient for the other. However, once arch primordia are established the effects of BMPs become restricted to more ventral and anterior (palate) domains, which do not depend on Edn1. This suggests that BMPs act upstream and in parallel to Edn1 to promote ventral fates in the arches during early DV patterning, but later acquire distinct roles that further subdivide the identities of NC cells to pattern the craniofacial skeleton.

AB - SUMMARY Bone morphogenetic proteins (BMPs) play crucial roles in craniofacial development but little is known about their interactions with other signals, such as Endothelin 1 (Edn1) and Jagged/Notch, which pattern the dorsal-ventral (DV) axis of the pharyngeal arches. Here, we use transgenic zebrafish to monitor and perturb BMP signaling during arch formation. With a BMP-responsive transgene, Tg(Bre:GFP), we show active BMP signaling in neural crest (NC)-derived skeletal precursors of the ventral arches, and in surrounding epithelia. Loss-of-function studies using a heat shock-inducible, dominant-negative BMP receptor 1a [Tg(hs70I:dnBmpr1a-GFP)] to bypass early roles show that BMP signaling is required for ventral arch development just after NC migration, the same stages at which we detect Tg(Bre:GFP). Inhibition of BMP signaling at these stages reduces expression of the ventral signal Edn1, as well as ventral-specific genes such as hand2 and dlx6a in the arches, and expands expression of the dorsal signal jag1b. This results in a loss or reduction of ventral and intermediate skeletal elements and a mis-shapen dorsal arch skeleton. Conversely, ectopic BMP causes dorsal expansion of ventral-specific gene expression and corresponding reductions/transformations of dorsal cartilages. Soon after NC migration, BMP is required to induce Edn1 and overexpression of either signal partially rescues ventral skeletal defects in embryos deficient for the other. However, once arch primordia are established the effects of BMPs become restricted to more ventral and anterior (palate) domains, which do not depend on Edn1. This suggests that BMPs act upstream and in parallel to Edn1 to promote ventral fates in the arches during early DV patterning, but later acquire distinct roles that further subdivide the identities of NC cells to pattern the craniofacial skeleton.

KW - Branchial arch

KW - Craniofacial

KW - Neural crest

KW - Pharyngeal arch

KW - Xenopus

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=80755148792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80755148792&partnerID=8YFLogxK

U2 - 10.1242/dev.067801

DO - 10.1242/dev.067801

M3 - Article

VL - 138

SP - 5135

EP - 5146

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 23

ER -