Programmed Cell Death Is Required for Palate Shelf Fusion and Is Regulated by Retinoic Acid

The actual role of programmed cell death (PCD) in embryonic processes and the extrinsic signals that define the death fate in developing cells are still poorly understood. Here, we show that during secondary palate shelf fusion in the mouse, PCD appeared in the medial edge epithelia (MEE) of the ant...

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Bibliographic Details
Published in:Developmental biology 2002-05, Vol.245 (1), p.145-156
Main Authors: Cuervo, Rodrigo, Valencia, Concepción, Chandraratna, Roshantha A.S., Covarrubias, Luis
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Apoptosis - physiology
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins - physiology
Cleft Palate - chemically induced
Female
Gene Expression Regulation, Developmental - drug effects
In Situ Hybridization
Mice
Palate - drug effects
Palate - embryology
palate development
Pregnancy
programmed cell death
retinoic acid
tissue fusion
Transforming Growth Factor beta - genetics
Tretinoin - pharmacology
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Summary:The actual role of programmed cell death (PCD) in embryonic processes and the extrinsic signals that define the death fate in developing cells are still poorly understood. Here, we show that during secondary palate shelf fusion in the mouse, PCD appeared in the medial edge epithelia (MEE) of the anterior region only after shelf contact. Contact was necessary for efficient cell death activation in the MEE. However, exogenous all-trans-retinoic acid (RA) increased cell death independently of contact. Competence to induce cell death by contact or by RA exposure was obtained when the MEE were close to touch. Endogenous RA is a relevant regulator of the secondary palate PCD since this was reduced by a retinol dehydrogenase inhibitor and an RAR specific antagonist. Bmp-7 expression was positively regulated by RA. However, BMP-7 was unable to activate cell death within the palate tissue and NOGGIN, a natural BMP antagonist, did not block PCD. Reduction of PCD at the MEE directly with a caspase inhibitor or by inhibiting retinol dehydrogenase resulted in unfused palate shelves, but adhesion was not affected. In contrast, exogenous RA also blocked fusion, but in this situation the increased cell death within the MEE appeared to affect adhesion, thereby causing cleft palate in vivo.
ISSN:0012-1606
1095-564X
DOI:10.1006/dbio.2002.0620