title: Meis2 is essential for cranial and cardiac neural crest development.
abstract: BACKGROUND
  TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging.
  
  
  RESULTS
  We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities.
  
  
  CONCLUSIONS
  Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.
authors.affiliation: Institute of Molecular Genetics, The Czech Academy of Sciences, 14200, Praha, Czech Republic. machon@img.cas.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Machon
authors.affiliation: Institute of Molecular Genetics, The Czech Academy of Sciences, 14200, Praha, Czech Republic. jan.masek@img.cas.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Masek
authors.affiliation: Institute of Molecular Genetics, The Czech Academy of Sciences, 14200, Praha, Czech Republic. olga.machonova@img.cas.cz.
authors.forename: Olga
authors.initials: O
authors.lastname: Machonova
authors.affiliation: Unit for Cell Signaling, Oslo University Hospital, N-0349, Oslo, Norway. stefan.krauss@rr-research.no.
authors.forename: Stefan
authors.initials: S
authors.lastname: Krauss
authors.affiliation: Institute of Molecular Genetics, The Czech Academy of Sciences, 14200, Praha, Czech Republic. zbynek.kozmik@img.cas.cz.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Kozmik
mesh_terms: D000818:Animals; D002356:Cartilage / Q000002:abnormalities / Q000196:embryology; D003391:Cranial Nerves / Q000196:embryology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics; D006470:Hemorrhage / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D012886:Skull / Q000196:embryology* / Q000294:innervation
chemical_list: D051858:Forkhead Transcription Factors; C101757:Foxd3 protein, mouse; D018398:Homeodomain Proteins; C102641:Mrg1 protein, mouse; D012097:Repressor Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse