Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis.

Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Research Abstract Details 

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Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Abstract Text:

Zunyi Zhang,Yiqiang Song,Xiang Zhao,Xiaoyun Zhang,Cesar Fermin,YiPing Chen,

Cleft palate, the most frequent congenital craniofacial birth defects in humans, arises from genetic or environmental perturbations in the multi-step process of palate development. Mutations in the MSX1 homeobox gene are associated with non-syndromic cleft palate and tooth agenesis in humans. We have used Msx1-deficient mice as a model system that exhibits severe craniofacial abnormalities, including cleft secondary palate and lack of teeth, to study the genetic regulation of mammalian palatogenesis. We found that Msx1 expression was restricted to the anterior of the first upper molar site in the palatal mesenchyme and that Msx1 was required for the expression of Bmp4 and Bmp2 in the mesenchyme and Shh in the medial edge epithelium (MEE) in the same region of developing palate. In vivo and in vitro analyses indicated that the cleft palate seen in Msx1 mutants resulted from a defect in cell proliferation in the anterior palatal mesenchyme rather than a failure in palatal fusion. Transgenic expression of human Bmp4 driven by the mouse Msx1 promoter in the Msx1(-/-) palatal mesenchyme rescued the cleft palate phenotype and neonatal lethality. Associated with the rescue of the cleft palate was a restoration of Shh and Bmp2 expression, as well as a return of cell proliferation to the normal levels. Ectopic Bmp4 appears to bypass the requirement for Msx1 and functions upstream of Shh and Bmp2 to support palatal development. Further in vitro assays indicated that Shh (normally expressed in the MEE) activates Bmp2 expression in the palatal mesenchyme which in turn acts as a mitogen to stimulate cell division. Msx1 thus controls a genetic hierarchy involving BMP and Shh signals that regulates the growth of the anterior region of palate during mammalian palatogenesis. Our findings provide insights into the cellular and molecular etiology of the non-syndromic clefting associated with Msx1 mutations.

Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Publishing Authors By Initials

Z Zhang,Y Song,X Zhao,X Zhang,C Fermin,Y Chen,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Development (Cambridge, England)

VOLUME: 129

Page Numbers: 4135-46

Journal Abbreviation: Development

ISSN: 0950-1991

DAY: 19

MONTH: Sep

YEAR: 2002

Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Information

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LANGUAGE: eng

NlmUniqueID: 8701744

Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: metabolism

Chemical & Substance for Abstract: Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Information

Substance Name: bone morphogenetic protein 4

Registry Number: 0

Grant and Affiliation Information for Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis.

AFFILIATION: Department of Cell and Molecular Biology and Center for Bioenvironmental Research, Tulane University, New Orleans, LA 70118, USA.

Country: England

AGENCY: United States NIDCR

GRANT: R01DE14044

ACRONYM: DE

MEDLINETA: Development

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