Affordable Access

deepdyve-link
Publisher Website

Control of growth and gut maturation by HoxD genes and the associated lncRNA Haglr.

Authors
  • Zakany, Jozsef1
  • Darbellay, Fabrice2
  • Mascrez, Bénédicte1
  • Necsulea, Anamaria2
  • Duboule, Denis3, 2
  • 1 Department of Genetics and Evolution, University of Geneva, 1211 Geneva 4, Switzerland. , (Switzerland)
  • 2 School of Life Sciences, Federal Institute of Technology, Lausanne (EPFL), 1015 Lausanne, Switzerland. , (Switzerland)
  • 3 Department of Genetics and Evolution, University of Geneva, 1211 Geneva 4, Switzerland; [email protected] , (Switzerland)
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Oct 31, 2017
Volume
114
Issue
44
Identifiers
DOI: 10.1073/pnas.1712511114
PMID: 29042517
Source
Medline
Keywords
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times