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Regulatory integration of Hox factor activity with Tbox factors in limb development.

Authors :
Jain, Deepak
Nemec, Stephen
Luxey, Maëva
Gauthier, Yves
Bemmo, Amandine
Balsalobre, Aurelio
Drouin, Jacques
Source :
Development (09501991). 3/1/2018, Vol. 145 Issue 5, p1-50. 50p.
Publication Year :
2018

Abstract

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 colocalized 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. [ABSTRACT FROM AUTHOR]

Subjects

Subjects :
*TETRAPODS
*GENES
*REPORTER genes

Details

Language :
English
ISSN :
09501991
Volume :
145
Issue :
5
Database :
Academic Search Index
Journal :
Development (09501991)
Publication Type :
Academic Journal
Accession number :
128402229
Full Text :
https://doi.org/10.1242/dev.159830