Augmented BMP signaling in the neural crest inhibits nasal cartilage morphogenesis by inducing p53-mediated apoptosis

Development
Satoru HayanoYuji Mishina

Abstract

Bone morphogenetic protein (BMP) signaling plays many roles in skull morphogenesis. We have previously reported that enhanced BMP signaling through the BMP type IA receptor (BMPR1A) in cranial neural crest cells causes craniosynostosis during postnatal development. Additionally, we observed that 55% of Bmpr1a mutant mice show neonatal lethality characterized by a distended gastrointestinal tract. Here, we show that severely affected mutants exhibit defective nasal cartilage, failure of fusion between the nasal septum and the secondary palate, and higher levels of phosphorylated SMAD1 and SMAD5 in the nasal tissue. TUNEL demonstrated an increase in apoptosis in both condensing mesenchymal tissues and cartilage of the nasal region in mutants. The levels of p53 (TRP53) tumor suppressor protein were also increased in the same tissue. Injection of pifithrin-α, a chemical inhibitor of p53, into pregnant mice prevented neonatal lethality while concomitantly reducing apoptosis in nasal cartilage primordia, suggesting that enhanced BMP signaling induces p53-mediated apoptosis in the nasal cartilage. The expression of Bax and caspase 3, downstream targets of p53, was increased in the mutants; however, the p53 expression level was unchang...Continue Reading

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Citations

Jan 10, 2016·Cytokine & Growth Factor Reviews·Daniel GrafYuji Mishina
Jan 25, 2016·Cytokine & Growth Factor Reviews·Christian HiepenPetra Knaus
Jul 30, 2015·Genesis : the Journal of Genetics and Development·Honghao ZhangYuji Mishina
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Aug 23, 2018·Genesis : the Journal of Genetics and Development·Kaitrin KramerYuji Mishina
Sep 26, 2020·Journal of Structural Biology·Amel DudakovicNan E Hatch

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