Menin is required in cranial neural crest for palatogenesis and perinatal viability.
Menin is a nuclear protein encoded by a tumor suppressor gene that is mutated in humans with multiple endocrine neoplasia type 1 (MEN1). Menin functions as a component of a histone methyltransferase complex that regulates expression of target genes including the cell cycle inhibitor p27(kip1). Here, we show that menin plays a previously unappreciated and critical role in cranial neural crest. Tissue-specific inactivation of menin in Pax3- or Wnt1-expressing neural crest cells leads to perinatal death, cleft palate and other cranial bone defects, which are associated with a decrease in p27(kip1) expression. Deletion of menin in Pax3-expressing somite precursors also produces patterning defects of rib formation. Thus, menin functions in vivo during osteogenesis and is required for palatogenesis, skeletal rib formation and perinatal viability.
Engleka
Kurt A
KA
Department of Cell and Developmental Biology and the Cardiovascular Institute, University of Pennsylvania, 1154 BRB II, 421 Curie Blvd, Philadelphia, PA 19104, USA.
Wu
Meilin
M
Zhang
Maozhen
M
Antonucci
Nicole B
NB
Epstein
Jonathan A
JA
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002972:Cleft Palate; D046689:Fetal Mortality; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009432:Neural Crest / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D010159:Palate / Q000196:embryology / Q000254:growth & development; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
C484898:Men1 protein, mouse; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C068686:Pax3 protein, mouse