Runx2 function in cells of neural crest origin during intramembranous ossification

Yukako Shirai, Kenji Kawabe, Ikue Tosa, Shunpei Tsukamoto, Daisuke Yamada, Takeshi Takarada

Research output: Contribution to journalArticle

Abstract

Runt-related transcription factor 2 (Runx2), also known as core binding factor 1 (Cbfa1), is a multifunctional transcription factor and an essential master gene controlling osteoblast differentiation. We previously demonstrated the in vivo functions of Runx2 in mesoderm-derived cells. However, no studies have been conducted on Runx2 function during the differentiation of neural crest (NC)-derived cells in vivo. Wingless-type MMTV integration site family member 1 (Wnt1) is expressed in the NC, and Wnt1-Cre efficiently targets craniofacial NC-derived cells. Runx2 deficiency in cells of the Wnt1 lineage (referred henceforth as Runx2wnt1 −/− within mice) resulted in defective ossification in certain regions, primarily in the anterior half of the craniofacial bones, including the frontal bone, jugal bone, squamous temporal bone, mandible, maxilla, and nasal bone. The skeletal analysis also revealed that heterozygous Runx2wnt1 +/− embryos had an impaired closure of the frontal bone at the metopic suture and lacked the secondary palate in spite of otherwise normal ossification. This result suggests that ossification at the central part of the frontal bone is more dependent on Runx2 expression in comparison to other areas. These results indicate that Runx2 is indispensable not only for mesoderm-derived cells but also for NC-derived cells to differentiate during intramembranous ossification after migration to their destination from the neural plate border. Moreover, this implies that there are different levels of dependency on Runx2 expression for successful ossification between NC-derived cells that have migrated to different locations.

Original languageEnglish
Pages (from-to)1028-1033
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume509
Issue number4
DOIs
Publication statusPublished - Feb 19 2019

Fingerprint

Neural Crest
Osteogenesis
Frontal Bone
Bone
Mesoderm
Transcription Factors
Core Binding Factors
Nasal Bone
Zygoma
Neural Plate
Bone and Bones
Palate
Temporal Bone
Essential Genes
Maxilla
Cell Lineage
Osteoblasts
Mandible
Sutures
Embryonic Structures

Keywords

  • Craniofacial ossification
  • Frontal bone
  • Neural crest
  • Runx2
  • wnt1-cre

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Runx2 function in cells of neural crest origin during intramembranous ossification. / Shirai, Yukako; Kawabe, Kenji; Tosa, Ikue; Tsukamoto, Shunpei; Yamada, Daisuke; Takarada, Takeshi.

In: Biochemical and Biophysical Research Communications, Vol. 509, No. 4, 19.02.2019, p. 1028-1033.

Research output: Contribution to journalArticle

Shirai, Yukako ; Kawabe, Kenji ; Tosa, Ikue ; Tsukamoto, Shunpei ; Yamada, Daisuke ; Takarada, Takeshi. / Runx2 function in cells of neural crest origin during intramembranous ossification. In: Biochemical and Biophysical Research Communications. 2019 ; Vol. 509, No. 4. pp. 1028-1033.
@article{33e244b65dc34d40864bf5a4574b6850,
title = "Runx2 function in cells of neural crest origin during intramembranous ossification",
abstract = "Runt-related transcription factor 2 (Runx2), also known as core binding factor 1 (Cbfa1), is a multifunctional transcription factor and an essential master gene controlling osteoblast differentiation. We previously demonstrated the in vivo functions of Runx2 in mesoderm-derived cells. However, no studies have been conducted on Runx2 function during the differentiation of neural crest (NC)-derived cells in vivo. Wingless-type MMTV integration site family member 1 (Wnt1) is expressed in the NC, and Wnt1-Cre efficiently targets craniofacial NC-derived cells. Runx2 deficiency in cells of the Wnt1 lineage (referred henceforth as Runx2wnt1 −/− within mice) resulted in defective ossification in certain regions, primarily in the anterior half of the craniofacial bones, including the frontal bone, jugal bone, squamous temporal bone, mandible, maxilla, and nasal bone. The skeletal analysis also revealed that heterozygous Runx2wnt1 +/− embryos had an impaired closure of the frontal bone at the metopic suture and lacked the secondary palate in spite of otherwise normal ossification. This result suggests that ossification at the central part of the frontal bone is more dependent on Runx2 expression in comparison to other areas. These results indicate that Runx2 is indispensable not only for mesoderm-derived cells but also for NC-derived cells to differentiate during intramembranous ossification after migration to their destination from the neural plate border. Moreover, this implies that there are different levels of dependency on Runx2 expression for successful ossification between NC-derived cells that have migrated to different locations.",
keywords = "Craniofacial ossification, Frontal bone, Neural crest, Runx2, wnt1-cre",
author = "Yukako Shirai and Kenji Kawabe and Ikue Tosa and Shunpei Tsukamoto and Daisuke Yamada and Takeshi Takarada",
year = "2019",
month = "2",
day = "19",
doi = "10.1016/j.bbrc.2019.01.059",
language = "English",
volume = "509",
pages = "1028--1033",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Runx2 function in cells of neural crest origin during intramembranous ossification

AU - Shirai, Yukako

AU - Kawabe, Kenji

AU - Tosa, Ikue

AU - Tsukamoto, Shunpei

AU - Yamada, Daisuke

AU - Takarada, Takeshi

PY - 2019/2/19

Y1 - 2019/2/19

N2 - Runt-related transcription factor 2 (Runx2), also known as core binding factor 1 (Cbfa1), is a multifunctional transcription factor and an essential master gene controlling osteoblast differentiation. We previously demonstrated the in vivo functions of Runx2 in mesoderm-derived cells. However, no studies have been conducted on Runx2 function during the differentiation of neural crest (NC)-derived cells in vivo. Wingless-type MMTV integration site family member 1 (Wnt1) is expressed in the NC, and Wnt1-Cre efficiently targets craniofacial NC-derived cells. Runx2 deficiency in cells of the Wnt1 lineage (referred henceforth as Runx2wnt1 −/− within mice) resulted in defective ossification in certain regions, primarily in the anterior half of the craniofacial bones, including the frontal bone, jugal bone, squamous temporal bone, mandible, maxilla, and nasal bone. The skeletal analysis also revealed that heterozygous Runx2wnt1 +/− embryos had an impaired closure of the frontal bone at the metopic suture and lacked the secondary palate in spite of otherwise normal ossification. This result suggests that ossification at the central part of the frontal bone is more dependent on Runx2 expression in comparison to other areas. These results indicate that Runx2 is indispensable not only for mesoderm-derived cells but also for NC-derived cells to differentiate during intramembranous ossification after migration to their destination from the neural plate border. Moreover, this implies that there are different levels of dependency on Runx2 expression for successful ossification between NC-derived cells that have migrated to different locations.

AB - Runt-related transcription factor 2 (Runx2), also known as core binding factor 1 (Cbfa1), is a multifunctional transcription factor and an essential master gene controlling osteoblast differentiation. We previously demonstrated the in vivo functions of Runx2 in mesoderm-derived cells. However, no studies have been conducted on Runx2 function during the differentiation of neural crest (NC)-derived cells in vivo. Wingless-type MMTV integration site family member 1 (Wnt1) is expressed in the NC, and Wnt1-Cre efficiently targets craniofacial NC-derived cells. Runx2 deficiency in cells of the Wnt1 lineage (referred henceforth as Runx2wnt1 −/− within mice) resulted in defective ossification in certain regions, primarily in the anterior half of the craniofacial bones, including the frontal bone, jugal bone, squamous temporal bone, mandible, maxilla, and nasal bone. The skeletal analysis also revealed that heterozygous Runx2wnt1 +/− embryos had an impaired closure of the frontal bone at the metopic suture and lacked the secondary palate in spite of otherwise normal ossification. This result suggests that ossification at the central part of the frontal bone is more dependent on Runx2 expression in comparison to other areas. These results indicate that Runx2 is indispensable not only for mesoderm-derived cells but also for NC-derived cells to differentiate during intramembranous ossification after migration to their destination from the neural plate border. Moreover, this implies that there are different levels of dependency on Runx2 expression for successful ossification between NC-derived cells that have migrated to different locations.

KW - Craniofacial ossification

KW - Frontal bone

KW - Neural crest

KW - Runx2

KW - wnt1-cre

UR - http://www.scopus.com/inward/record.url?scp=85059950975&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059950975&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2019.01.059

DO - 10.1016/j.bbrc.2019.01.059

M3 - Article

C2 - 30660360

AN - SCOPUS:85059950975

VL - 509

SP - 1028

EP - 1033

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -