Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication

Ping Kong, Silvia Racedo, Stephania Macchiarulo, Zunju Hu, Courtney Carpenter, Tingwei Guo, Tao Wang, Deyou Zheng, Bernice E. Morrow

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Velo-cardio-facial/DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a congenital anomaly disorder characterized by craniofacial anomalies including velo-pharyngeal insufficiency, facial muscle hypotonia and feeding difficulties, in part due to hypoplasia of the branchiomeric muscles. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on chromosome 22q11.2, results in reduction or loss of branchiomeric muscles. To identify downstream pathways, we performed gene profiling of microdissected pharyngeal arch one (PA1) from Tbx1+/+ and Tbx1-/- embryos at stages E9.5 (somites 20-25) and E10.5 (somites 30-35). Basic helix-loop-helix (bHLH) transcription factors were reduced, while secondary heart field genes were increased in expression early and were replaced by an increase in expression of cellular stress response genes later, suggesting a change in gene expression patterns or cell populations. Lineage tracing studies using Mesp1Creand T-Cre drivers showed that core mesoderm cells with in PA1 were present at E9.5 but were greatly reduced by E10.5 in Tbx1-/- embryos. Using Tbx1Cre knock-in mice, we found that cells are lost due to apoptosis, consistent with increase in expression of cellular stress response genes at E10.5. To determine whether Tbx1 is required autonomously in the core mesoderm, we used Mesp1Cre and T-Cre mesodermal drivers in combination with inactivate Tbx1 and found reduction or loss of branchiomeric muscles from PA1. These mechanistic studies inform us that Tbx1 is required upstream of key myogenic genes needed for core mesoderm cell survival and fate, between E9.5 and E10.5, resulting in formation of the branchiomeric muscles.

Original languageEnglish (US)
Article numberddu140
Pages (from-to)4215-4231
Number of pages17
JournalHuman Molecular Genetics
Volume23
Issue number16
DOIs
StatePublished - 2014

Fingerprint

Mastication
Mesoderm
Cell Survival
DiGeorge Syndrome
Muscles
Somites
Genes
Embryonic Structures
Facial Muscles
Branchial Region
Basic Helix-Loop-Helix Transcription Factors
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Muscle Hypotonia
Transcription Factors
Chromosomes
Alleles
Apoptosis
Gene Expression
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication. / Kong, Ping; Racedo, Silvia; Macchiarulo, Stephania; Hu, Zunju; Carpenter, Courtney; Guo, Tingwei; Wang, Tao; Zheng, Deyou; Morrow, Bernice E.

In: Human Molecular Genetics, Vol. 23, No. 16, ddu140, 2014, p. 4215-4231.

Research output: Contribution to journalArticle

@article{2c6afbb2d80349dda1fc325500c9fe6d,
title = "Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication",
abstract = "Velo-cardio-facial/DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a congenital anomaly disorder characterized by craniofacial anomalies including velo-pharyngeal insufficiency, facial muscle hypotonia and feeding difficulties, in part due to hypoplasia of the branchiomeric muscles. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on chromosome 22q11.2, results in reduction or loss of branchiomeric muscles. To identify downstream pathways, we performed gene profiling of microdissected pharyngeal arch one (PA1) from Tbx1+/+ and Tbx1-/- embryos at stages E9.5 (somites 20-25) and E10.5 (somites 30-35). Basic helix-loop-helix (bHLH) transcription factors were reduced, while secondary heart field genes were increased in expression early and were replaced by an increase in expression of cellular stress response genes later, suggesting a change in gene expression patterns or cell populations. Lineage tracing studies using Mesp1Creand T-Cre drivers showed that core mesoderm cells with in PA1 were present at E9.5 but were greatly reduced by E10.5 in Tbx1-/- embryos. Using Tbx1Cre knock-in mice, we found that cells are lost due to apoptosis, consistent with increase in expression of cellular stress response genes at E10.5. To determine whether Tbx1 is required autonomously in the core mesoderm, we used Mesp1Cre and T-Cre mesodermal drivers in combination with inactivate Tbx1 and found reduction or loss of branchiomeric muscles from PA1. These mechanistic studies inform us that Tbx1 is required upstream of key myogenic genes needed for core mesoderm cell survival and fate, between E9.5 and E10.5, resulting in formation of the branchiomeric muscles.",
author = "Ping Kong and Silvia Racedo and Stephania Macchiarulo and Zunju Hu and Courtney Carpenter and Tingwei Guo and Tao Wang and Deyou Zheng and Morrow, {Bernice E.}",
year = "2014",
doi = "10.1093/hmg/ddu140",
language = "English (US)",
volume = "23",
pages = "4215--4231",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "16",

}

TY - JOUR

T1 - Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication

AU - Kong, Ping

AU - Racedo, Silvia

AU - Macchiarulo, Stephania

AU - Hu, Zunju

AU - Carpenter, Courtney

AU - Guo, Tingwei

AU - Wang, Tao

AU - Zheng, Deyou

AU - Morrow, Bernice E.

PY - 2014

Y1 - 2014

N2 - Velo-cardio-facial/DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a congenital anomaly disorder characterized by craniofacial anomalies including velo-pharyngeal insufficiency, facial muscle hypotonia and feeding difficulties, in part due to hypoplasia of the branchiomeric muscles. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on chromosome 22q11.2, results in reduction or loss of branchiomeric muscles. To identify downstream pathways, we performed gene profiling of microdissected pharyngeal arch one (PA1) from Tbx1+/+ and Tbx1-/- embryos at stages E9.5 (somites 20-25) and E10.5 (somites 30-35). Basic helix-loop-helix (bHLH) transcription factors were reduced, while secondary heart field genes were increased in expression early and were replaced by an increase in expression of cellular stress response genes later, suggesting a change in gene expression patterns or cell populations. Lineage tracing studies using Mesp1Creand T-Cre drivers showed that core mesoderm cells with in PA1 were present at E9.5 but were greatly reduced by E10.5 in Tbx1-/- embryos. Using Tbx1Cre knock-in mice, we found that cells are lost due to apoptosis, consistent with increase in expression of cellular stress response genes at E10.5. To determine whether Tbx1 is required autonomously in the core mesoderm, we used Mesp1Cre and T-Cre mesodermal drivers in combination with inactivate Tbx1 and found reduction or loss of branchiomeric muscles from PA1. These mechanistic studies inform us that Tbx1 is required upstream of key myogenic genes needed for core mesoderm cell survival and fate, between E9.5 and E10.5, resulting in formation of the branchiomeric muscles.

AB - Velo-cardio-facial/DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a congenital anomaly disorder characterized by craniofacial anomalies including velo-pharyngeal insufficiency, facial muscle hypotonia and feeding difficulties, in part due to hypoplasia of the branchiomeric muscles. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on chromosome 22q11.2, results in reduction or loss of branchiomeric muscles. To identify downstream pathways, we performed gene profiling of microdissected pharyngeal arch one (PA1) from Tbx1+/+ and Tbx1-/- embryos at stages E9.5 (somites 20-25) and E10.5 (somites 30-35). Basic helix-loop-helix (bHLH) transcription factors were reduced, while secondary heart field genes were increased in expression early and were replaced by an increase in expression of cellular stress response genes later, suggesting a change in gene expression patterns or cell populations. Lineage tracing studies using Mesp1Creand T-Cre drivers showed that core mesoderm cells with in PA1 were present at E9.5 but were greatly reduced by E10.5 in Tbx1-/- embryos. Using Tbx1Cre knock-in mice, we found that cells are lost due to apoptosis, consistent with increase in expression of cellular stress response genes at E10.5. To determine whether Tbx1 is required autonomously in the core mesoderm, we used Mesp1Cre and T-Cre mesodermal drivers in combination with inactivate Tbx1 and found reduction or loss of branchiomeric muscles from PA1. These mechanistic studies inform us that Tbx1 is required upstream of key myogenic genes needed for core mesoderm cell survival and fate, between E9.5 and E10.5, resulting in formation of the branchiomeric muscles.

UR - http://www.scopus.com/inward/record.url?scp=84904767584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904767584&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu140

DO - 10.1093/hmg/ddu140

M3 - Article

VL - 23

SP - 4215

EP - 4231

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 16

M1 - ddu140

ER -