Title: Noggin null allele mice exhibit a microform of holoprosencephaly
Authors: Lana-Elola, Eva
Tylzanowski, Przemyslaw
Takatalo, Maarit
Alakurtti, Kirsi
Veistinen, Lotta
Mitsiadis, Thimios A
Graf, Daniel
Rice, Ritva
Luyten, Frank
Rice, David P # ×
Issue Date: Aug-2011
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:20 issue:20 pages:4005-4015
Abstract: Holoprosencephaly (HPE) is a heterogeneous craniofacial and neural developmental anomaly characterized in its most severe form by the failure of the forebrain to divide. In humans, HPE is associated with disruption of Sonic hedgehog and Nodal signaling pathways, but the role of other signaling pathways has not yet been determined. In this study, we analyzed mice which, due to the lack of the Bmp antagonist Noggin, exhibit elevated Bmp signaling. Noggin(-/-) mice exhibited a solitary median maxillary incisor that developed from a single dental placode, early midfacial narrowing as well as abnormalities in the developing hyoid bone, pituitary gland and vomeronasal organ. In Noggin(-/-) mice, the expression domains of Shh, as well as the Shh target genes Ptch1 and Gli1, were reduced in the frontonasal region at key stages of early facial development. Using E10.5 facial cultures, we show that excessive BMP4 results in reduced Fgf8 and Ptch1 expression. These data suggest that increased Bmp signaling in Noggin(-/-) mice results in downregulation of the hedgehog pathway at a critical stage when the midline craniofacial structures are developing, which leads to a phenotype consistent with a microform of HPE.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Rheumatology Section (-)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science