Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects.

Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects. Research Abstract Details 

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Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects. Abstract Text:

Xuguang Nie,Chu-xia Deng,Qin Wang,Kai Jiao,

TGFbeta/BMP signaling pathways are essential for normal development of neural crest cells (NCCs). Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of TGFbeta/BMP signaling. In this work, we sought to investigate the roles of Smad4 for development of NCCs. To overcome the early embryonic lethality of Smad4 null mice, we specifically disrupted Smad4 in NCCs using a Cre/loxP system. The mutant mice died at mid-gestation with defects in facial primordia, pharyngeal arches, outflow tract and cardiac ventricles. Further examination revealed that mutant embryos displayed severe molecular defects starting from E9.5. Expression of multiple genes, including Msx1, 2, Ap-2 alpha, Pax3, and Sox9, which play critical roles for NCC development, was downregulated by NCC disruption of Smad4. Moreover, increased cell death was observed in pharyngeal arches from E10.5. However, the cell proliferation rate in these areas was not substantially altered. Taken together, these findings provide compelling genetic evidence that Smad4-mediated activities of TGFbeta/BMP signals are essential for appropriate NCC development.

Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects. Publishing Authors By Initials

X Nie,CX Deng,Q Wang,K Jiao,

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Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Developmental biology

VOLUME: 316

Page Numbers: 417-30

Journal Abbreviation: Dev. Biol.

ISSN: 1095-564X

DAY: 15

MONTH: 02

YEAR: 2008

Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects. Information

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LANGUAGE: eng

NlmUniqueID: 372762

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Grant and Affiliation Information for Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects.

AFFILIATION: Department of Genetics, Division of Genetic and Translational Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: 1R21HL085510-01

ACRONYM: HL

MEDLINETA: Dev Biol

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