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Publication : Control of growth and gut maturation by <i>HoxD</i> genes and the associated lncRNA <i>Haglr</i>.

First Author  Zakany J Year  2017
Journal  Proc Natl Acad Sci U S A Volume  114
Issue  44 Pages  E9290-E9299
PubMed ID  29042517 Mgi Jnum  J:252916
Mgi Id  MGI:6095333 Doi  10.1073/pnas.1712511114
Citation  Zakany J, et al. (2017) Control of growth and gut maturation by HoxD genes and the associated lncRNA Haglr. Proc Natl Acad Sci U S A 114(44):E9290-E9299
abstractText  During embryonic development, Hox genes participate in the building of a functional digestive system in metazoans, and genetic conditions involving these genes lead to important, sometimes lethal, growth retardation. Recently, this phenotype was obtained after deletion of Haglr, the Hoxd antisense growth-associated long noncoding RNA (lncRNA) located between Hoxd1 and Hoxd3 In this study, we have analyzed the function of Hoxd genes in delayed growth trajectories by looking at several nested targeted deficiencies of the mouse HoxD cluster. Mutant pups were severely stunted during the suckling period, but many recovered after weaning. After comparing seven distinct HoxD alleles, including CRISPR/Cas9 deletions involving Haglr, we identified Hoxd3 as the critical component for the gut to maintain milk-digestive competence. This essential function could be abrogated by the dominant-negative effect of HOXD10 as shown by a genetic rescue approach, thus further illustrating the importance of posterior prevalence in Hox gene function. A role for the lncRNA Haglr in the control of postnatal growth could not be corroborated.
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