PT  - JOURNAL ARTICLE
AU  - Ma Félix Bastida
AU  - Rocío Pérez-Gómez
AU  - Anna Trofka
AU  - Rushikesh Sheth
AU  - H. Scott Stadler
AU  - Susan Mackem
AU  - Marian A. Ros
TI  - Mutual transcriptional repression between <em>Gli3</em> and <em>Hox13</em> genes determines the anterior-posterior asymmetry of the autopod
AID  - 10.1101/419606
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 419606
4099  - http://biorxiv.org/content/early/2018/09/17/419606.short
4100  - http://biorxiv.org/content/early/2018/09/17/419606.full
AB  - In the present study we have investigated the molecular causes of the absence of digit 1 in the Hoxa13 mutant and why the absence of Hoxa13 protein, whose expression spans the entire autopod, specifically impacts the anterior-most digit. We show that in the absence of Hoxa13, the expression of Hoxd13 does not extend into the anterior mesoderm consequently leaving the presumptive territory of digit1 devoid of distal Hox expression and providing an explanation for the agenesis of digit 1. We provide compelling evidence that the lack of Hoxd13 transcription in the anterior mesoderm is due to increased Gli3R activity, in turn resulting from the loss of transcriptional repression exerted by Hoxa13 on Gli3. Our results are compatible with a mutual transcriptional repression between Gli3 and Hox13 genes that determines the anterior-posterior asymmetry of the autopod.