Meis2 is essential for cranial and cardiac neural crest development

Abstract

BackgroundTALE-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.ResultsWe 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.ConclusionsMeis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-015-0093-6) contains supplementary material, which is available to authorized users.

The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of Pax6

“…We therefore questioned whether deletion of Meis2 may affect lens development. Accordingly, mice containing a Meis2 floxed allele ( Meis2 f/f ) were generated (S1G Fig) and [32], and subsequently zygotic Hprt1-Cre mice were employed to create whole-body knockout of Meis2 ( Meis2 -/- ). Meis2 -/- embryos displayed strong hemorrhage and other developmental defects and died by E14.5 [32].…”

“…A conditional mutant allele of the Meis2 gene ( Meis2 f/f ) was generated by inserting loxP sites in the introns 2 and 6, flanking exons 3 and 6 in the Meis2 gene (S1G Fig) at the Gene Targeting & Transgenic Facility, University of Connecticut, USA [32]. To generate whole-body knockout of Meis2 , Meis2 f/f mice were crossed with Hprt-Cre mice (strain 129S1/Sv-Hprt tm1(cre)Mnn /J, stock 004302, The Jackson Laboratory) that display the zygotic Cre recombinase activity.…”

The Multiple Signals That Control Tuber Formation

“…In plants, BEL1-like proteins function in a tandem complex with KNOX-type TFs to regulate numerous aspects of growth and development (Chen et al, 2003;Smith and Hake, 2003;Brambilla et al, 2007;Rutjens et al, 2009;Khan et al, 2012). Related genes from the TALE class in animals also control important processes of growth and differentiation (Machon et al, 2015;Marcos et al, 2015;Merabet and Galliot, 2015;Villaescusa et al, 2016). The physical interaction between KNOX and BEL1 proteins and its functional significance have been documented in numerous plant species (Bellaoui et al, 2001;Müller et al, 2001;Smith et al, 2002;Chen et al, 2003Chen et al, , 2004.…”

Prenatal diagnosis and molecular cytogenetic characterization of a de novo 4.858-Mb microdeletion in 15q14 associated with ACTC1 and MEIS2 haploinsufficiency and tetralogy of Fallot

“…Louw et al [21] reported a de novo small intragenic mutation in MEIS2 in a female patient with cleft palate, septal defects, aortic coarctation, facial dysmorphism, intellectual disability, and autism spectrum disorder, and suggested that MEIS2 is involved in cardiac development, cleft palate, and intellectual disability. Machon et al [22] demonstrated that MEIS2 plays a critical role during cranial and cardiac neural crest cell development in the mouse.…”