Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development

Lu Zhang; Aya Nomura-Kitabayashi; Nishat Sultana; Weibin Cai; Xiaoqiang Cai; Anne M. Moon; Chen Leng Cai

doi:10.1016/j.ydbio.2014.02.023

Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development

Lu Zhang
, Aya Nomura-Kitabayashi
, Nishat Sultana
, Weibin Cai
, Xiaoqiang Cai
, Anne M. Moon
, Chen Leng Cai

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

The vertebrate heart develops from mesoderm and requires inductive signals secreted from early endoderm. During embryogenesis, Nkx2.5 acts as a key transcription factor and plays essential roles for heart formation from Drosophila to human. In mice, Nkx2.5 is expressed in the early first heart field, second heart field pharyngeal mesoderm, as well as pharyngeal endodermal cells underlying the second heart field. Currently, the specific requirements for Nkx2.5 in the endoderm versus mesoderm with regard to early heart formation are incompletely understood. Here, we performed tissue-specific deletion in mice to dissect the roles of Nkx2.5 in the pharyngeal endoderm and mesoderm. We found that heart development appeared normal after endodermal deletion of Nkx2.5 whereas mesodermal deletion engendered cardiac defects almost identical to those observed on Nkx2.5 null embryos (Nkx2.5^-/-). Furthermore, re-expression of Nkx2.5 in the mesoderm rescued Nkx2.5^-/- heart defects. Our findings reveal that Nkx2.5 in the mesoderm is essential while endodermal expression is dispensable for early heart formation in mammals.

Original language	English
Pages (from-to)	68-79
Number of pages	12
Journal	Developmental Biology
Volume	390
Issue number	1
DOIs	https://doi.org/10.1016/j.ydbio.2014.02.023
State	Published - 1 Jun 2014

Keywords

Heart development
Nkx2.5
Pharyngeal endoderm
Pharyngeal mesoderm
Second heart field

Access to Document

10.1016/j.ydbio.2014.02.023

Cite this

@article{c6aaebd0fc374febb51d3e59598c5f21,

title = "Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development",

abstract = "The vertebrate heart develops from mesoderm and requires inductive signals secreted from early endoderm. During embryogenesis, Nkx2.5 acts as a key transcription factor and plays essential roles for heart formation from Drosophila to human. In mice, Nkx2.5 is expressed in the early first heart field, second heart field pharyngeal mesoderm, as well as pharyngeal endodermal cells underlying the second heart field. Currently, the specific requirements for Nkx2.5 in the endoderm versus mesoderm with regard to early heart formation are incompletely understood. Here, we performed tissue-specific deletion in mice to dissect the roles of Nkx2.5 in the pharyngeal endoderm and mesoderm. We found that heart development appeared normal after endodermal deletion of Nkx2.5 whereas mesodermal deletion engendered cardiac defects almost identical to those observed on Nkx2.5 null embryos (Nkx2.5-/-). Furthermore, re-expression of Nkx2.5 in the mesoderm rescued Nkx2.5-/- heart defects. Our findings reveal that Nkx2.5 in the mesoderm is essential while endodermal expression is dispensable for early heart formation in mammals.",

keywords = "Heart development, Nkx2.5, Pharyngeal endoderm, Pharyngeal mesoderm, Second heart field",

author = "Lu Zhang and Aya Nomura-Kitabayashi and Nishat Sultana and Weibin Cai and Xiaoqiang Cai and Moon, \{Anne M.\} and Cai, \{Chen Leng\}",

note = "Funding Information: The authors thank Drs. Yumiko Saga (National Institute of Genetics, Japan) and Ken Chien (MGH, Boston, USA) for their generosity in providing the Mesp 1 Cre /+ and Nkx 2.5 flox / flox mice, respectively. We are also very grateful to Dr. Bruce Gelb for critical reading of this manuscript, and Dr. Kevin Kelly in the Transgenic Core of Mount Sinai for generating mouse models. A.N.K is supported by an NIH T32 training grant. C.L.C. is supported by grants from the NIH/NHLBI ( 1R01HL095810 and 1K02HL094688 ), the American Heart Association ( 0855808D ) and the March of Dimes Foundation ( 5-FY07-642 ). ",

year = "2014",

month = jun,

day = "1",

doi = "10.1016/j.ydbio.2014.02.023",

language = "English",

volume = "390",

pages = "68--79",

journal = "Developmental Biology",

issn = "0012-1606",

publisher = "Elsevier Inc.",

number = "1",

}

TY - JOUR

T1 - Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development

AU - Zhang, Lu

AU - Nomura-Kitabayashi, Aya

AU - Sultana, Nishat

AU - Cai, Weibin

AU - Cai, Xiaoqiang

AU - Moon, Anne M.

AU - Cai, Chen Leng

N1 - Funding Information: The authors thank Drs. Yumiko Saga (National Institute of Genetics, Japan) and Ken Chien (MGH, Boston, USA) for their generosity in providing the Mesp 1 Cre /+ and Nkx 2.5 flox / flox mice, respectively. We are also very grateful to Dr. Bruce Gelb for critical reading of this manuscript, and Dr. Kevin Kelly in the Transgenic Core of Mount Sinai for generating mouse models. A.N.K is supported by an NIH T32 training grant. C.L.C. is supported by grants from the NIH/NHLBI ( 1R01HL095810 and 1K02HL094688 ), the American Heart Association ( 0855808D ) and the March of Dimes Foundation ( 5-FY07-642 ).

PY - 2014/6/1

Y1 - 2014/6/1

N2 - The vertebrate heart develops from mesoderm and requires inductive signals secreted from early endoderm. During embryogenesis, Nkx2.5 acts as a key transcription factor and plays essential roles for heart formation from Drosophila to human. In mice, Nkx2.5 is expressed in the early first heart field, second heart field pharyngeal mesoderm, as well as pharyngeal endodermal cells underlying the second heart field. Currently, the specific requirements for Nkx2.5 in the endoderm versus mesoderm with regard to early heart formation are incompletely understood. Here, we performed tissue-specific deletion in mice to dissect the roles of Nkx2.5 in the pharyngeal endoderm and mesoderm. We found that heart development appeared normal after endodermal deletion of Nkx2.5 whereas mesodermal deletion engendered cardiac defects almost identical to those observed on Nkx2.5 null embryos (Nkx2.5-/-). Furthermore, re-expression of Nkx2.5 in the mesoderm rescued Nkx2.5-/- heart defects. Our findings reveal that Nkx2.5 in the mesoderm is essential while endodermal expression is dispensable for early heart formation in mammals.

AB - The vertebrate heart develops from mesoderm and requires inductive signals secreted from early endoderm. During embryogenesis, Nkx2.5 acts as a key transcription factor and plays essential roles for heart formation from Drosophila to human. In mice, Nkx2.5 is expressed in the early first heart field, second heart field pharyngeal mesoderm, as well as pharyngeal endodermal cells underlying the second heart field. Currently, the specific requirements for Nkx2.5 in the endoderm versus mesoderm with regard to early heart formation are incompletely understood. Here, we performed tissue-specific deletion in mice to dissect the roles of Nkx2.5 in the pharyngeal endoderm and mesoderm. We found that heart development appeared normal after endodermal deletion of Nkx2.5 whereas mesodermal deletion engendered cardiac defects almost identical to those observed on Nkx2.5 null embryos (Nkx2.5-/-). Furthermore, re-expression of Nkx2.5 in the mesoderm rescued Nkx2.5-/- heart defects. Our findings reveal that Nkx2.5 in the mesoderm is essential while endodermal expression is dispensable for early heart formation in mammals.

KW - Heart development

KW - Nkx2.5

KW - Pharyngeal endoderm

KW - Pharyngeal mesoderm

KW - Second heart field

UR - https://www.scopus.com/pages/publications/84897572490

U2 - 10.1016/j.ydbio.2014.02.023

DO - 10.1016/j.ydbio.2014.02.023

M3 - Article

C2 - 24613616

AN - SCOPUS:84897572490

SN - 0012-1606

VL - 390

SP - 68

EP - 79

JO - Developmental Biology

JF - Developmental Biology

IS - 1

ER -

Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development

Abstract

Keywords

Access to Document

Fingerprint

Cite this