Rxivist logo

Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks

By Kelsey H Elliott, Xiaoting Chen, Joseph Salomone, Praneet Chaturvedi, Preston A Schultz, Sai K Balchand, Jeffrey D Servetas, Aimée Zuniga, Rolf Zeller, Brian Gebelein, Matthew T Weirauch, Kevin A. Peterson, Samantha A. Brugmann

Posted 15 Mar 2020
bioRxiv DOI: 10.1101/2020.03.13.990481 (published DOI: 10.7554/eLife.56450)

Despite a common understanding that Gli TFs are utilized to reiterate a Hh morphogen gradient, genetic analyses suggest craniofacial development does not completely fit this paradigm. We demonstrated that rather than being driven by a Hh threshold, robust Gli3 transcriptional activity during skeletal and glossal development required interaction with the bHLH TF Hand2. Not only did genetic and expression data support a co-factorial relationship, but genomic analysis further revealed that Gli3 and Hand2 were enriched at regulatory elements for genes essential for mandibular patterning and development. Interestingly, motif analysis at sites co-occupied by Gli3 and Hand2 uncovered mandibular-specific, low-affinity, 'divergent' Gli binding motifs (dGBMs). Functional validation revealed these dGBMs conveyed synergistic activation of Gli targets essential for mandibular patterning and development. In summary, this work elucidates a novel, sequence-dependent mechanism for Gli transcriptional activity within the craniofacial complex that is independent of a graded Hh signal.

Download data

  • Downloaded 335 times
  • Download rankings, all-time:
    • Site-wide: 70,849
    • In developmental biology: 1,875
  • Year to date:
    • Site-wide: 95,393
  • Since beginning of last month:
    • Site-wide: 60,735

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)