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.

Highlights

  • TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis

  • To generate mutant mice lacking functional Meis2 in the whole organism, Meis2 conditional knock-out (cKO) were at first crossed with the Hprt1-Cre mice (Jax Mice and Services) that exert a zygotic expression of Cre recombinase facilitating gene excision in all tissues

  • Meis2 cKO were crossed to Hprt-Cre mice (strain 129S1/Sv-Hprttm1(cre)Mnn/J, stock 004302, The Jackson Laboratory) with the zygotic activity of the Cre recombinase to obtain animals that were heterozygous for Meis2 (Meis2+/-) in the mixed genetic background

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Summary

Introduction

TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Neural crest cells (NCC) represent a multi-potent embryonic cell population that generates a very diverse range of cell types including cranial nerves, neurons and glia of the peripheral nervous system, enteric neurons, melanocytes, cranial bones and cartilages [1, 2]. As the neural tube closes in mouse, NCC delaminate from the regions of neural plate border and ectomesenchyme after epithelial-to-mesenchymal transition (EMT) and migrate to various developing organs. Meis proteins are transcription factors that are orthologous to the Drosophila homothorax (Hth) protein. They contain a TALE (three-amino-acid loop extension) sub-class of the homeodomain that binds to DNA.

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