De-coupling the Hox-Shh-Fgf interaction reveals multiple inputs of Hox genes on pathways ensuring limb growth

Resumen del trabajo presentado a los Congresos: 17th International Congress of Developmental Biology, 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting y XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo, celebrados en Cancún (México) del 16 al 20 de junio de 2013.-- et al.One of the most intriguing questions in developmental biology is how organ growth and patterning are coordinated during embryogenesis. Limb development relies on an exquisite coordination between growth and patterning but the underlying mechanisms remain elusive. Previous studies showed that A-P and P-D limb bud growth and patterning relies on a positive feedback loop between Sonic Hedgehog (Shh), the BMP antagonist Gremlin1 (Grem1), both expressed in mesenchymal cells, and Fibroblast growth factors (Fgfs) produced in the Apical Ectodermal Ridge (AER). In addition, the collinear expression of HoxA and HoxD genes has a key role in A-P and P-D patterning by establishing positional identity along these axes. Here, we show that HoxA and HoxD genes are required at early stages for Grem1 activation and proper Fgf10 and Fgf8 expression and therefore are mandatory for the establishment of the Shh-Grem1-Fgf feedback loop. Our results provide evidence that, in addition to this early function, HoxA and HoxD genes remain indispensable for proper limb growth at later stages. Together, our results reveal a dual role of Hox genes in controlling limb growth and establishing the limb architecture and we propose that the intricate interactions between Hox function and growth pathways act as the molecular network coordinating limb bud growth and patterning.Peer reviewe