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Developmental stalling and organ-autonomous regulation of morphogenesis.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2011 Nov 29; Vol. 108 (48), pp. 19270-5. Date of Electronic Publication: 2011 Nov 14. - Publication Year :
- 2011
-
Abstract
- Timing of organ development during embryogenesis is coordinated such that at birth, organ and fetal size and maturity are appropriately proportioned. The extent to which local developmental timers are integrated with each other and with the signaling interactions that regulate morphogenesis to achieve this end is not understood. Using the absolute requirement for a signaling pathway activity (bone morphogenetic protein, BMP) during a critical stage of tooth development, we show that suboptimal levels of BMP signaling do not lead to abnormal morphogenesis, as suggested by mutants affecting BMP signaling, but to a 24-h stalling of the intrinsic developmental clock of the tooth. During this time, BMP levels accumulate to reach critical levels whereupon tooth development restarts, accelerates to catch up with development of the rest of the embryo and completes normal morphogenesis. This suggests that individual organs can autonomously control their developmental timing to adjust their stage of development to that of other organs. We also find that although BMP signaling is critical for the bud-to-cap transition in all teeth, levels of BMP signaling are regulated differently in multicusped teeth. We identify an interaction between two homeodomain transcription factors, Barx1 and Msx1, which is responsible for setting critical levels of BMP activity in multicusped teeth and provides evidence that correlates the levels of Barx1 transcriptional activity with cuspal complexity. This study highlights the importance of absolute levels of signaling activity for development and illustrates remarkable self-regulation in organogenesis that ensures coordination of developmental processes such that timing is subordinate to developmental structure.
- Subjects :
- Age Factors
Animals
DNA Primers genetics
Fluorescent Antibody Technique
Humans
Immunoprecipitation
In Situ Hybridization
Mice
Mice, Knockout
X-Ray Microtomography
Bone Morphogenetic Proteins metabolism
Homeodomain Proteins metabolism
MSX1 Transcription Factor metabolism
Odontogenesis physiology
Signal Transduction physiology
Tooth embryology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 108
- Issue :
- 48
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 22084104
- Full Text :
- https://doi.org/10.1073/pnas.1112801108