Open AccessRegulatory integration of Hox factor activity with Tbox factors in limb development
Author(s) -
Deepak Jain,
Stephen Nemec,
Maëva Luxey,
Yves Gauthier,
Amandine Bemmo,
Aurélio Balsalobre,
Jacques Drouin
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.159830
Subject(s) - biology , hox gene , limb development , transcription factor , anatomy , computational biology , microbiology and biotechnology , genetics , gene
In tetrapods, Tbx4, Tbx5 and Hox cluster genes are crucial for forelimb and hindlimb development and mutations in these genes are responsible for congenital limb defects. The molecular basis of their integrated mechanisms of action in the context of limb development remains poorly understood. We studied Tbx4 and Hoxc10 due to their overlapping loss of function phenotypes and co-localized expression in hindlimb buds. We report an extensive overlap between Tbx4 and Hoxc10 genome occupancy and their putative target genes. Tbx4 and Hoxc10 interact directly with each other, have the ability to bind to a previously unrecognised Tbox-Hox composite DNA motif and show synergistic activity when acting on reporter genes. Pitx1, the master gene for hindlimb specification, also shows extensive genomic colocalization with Tbx4 and Hoxc10. Genome occupancy by Tbx4 in hindlimb buds is similar to Tbx5 occupancy in forelimbs. In contrast, another Hox factor, Hoxd13, also interacts with Tbx4/Tbx5 but Hoxd13 antagonises Tbx4/Tbx5-dependent transcriptional activity. Collectively, the modulation of Tbx-dependent activity by Hox factors acting on common DNA targets may integrate different developmental processes for balanced formation of proportionate limbs.