English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/130395

Decoupling the function of Hox and Shh in developing limb reveals multiple inputs of Hox genes on limb growth

AutorSheth, Rushikesh; Bastida, M. Félix ; Ros, María A. ; Kmita, Marie
Palabras claveMouse
Limb development
Gremlin 1
Hox genes
Organ growth
Fecha de publicación2013
EditorCompany of Biologists
CitaciónDevelopment 140(10): 2130-2138 (2013)
ResumenLimb development relies on an exquisite coordination between growth and patterning, but the underlying mechanisms remain elusive. Anterior-posterior and proximal-distal specification initiates in early limb bud concomitantly with the proliferative expansion of limb cells. Previous studies have shown that limb bud growth initially relies on fibroblast growth factors (FGFs) produced in the apical ectodermal ridge (AER-FGFs), the maintenance of which relies on a positive-feedback loop involving sonic hedgehog (Shh) and the BMP antagonist gremlin 1 (Grem1). The positive cross-regulation between Shh and the HoxA and HoxD clustered genes identified an indirect effect of Hox genes on the maintenance of AER-FGFs but the respective function of Shh and Hox genes in this process remains unknown. Here, by uncoupling Hox and Shh function, we show that HoxA and HoxD genes are required for proper AER-FGFs expression, independently of their function in controlling Shh expression. In addition, we provide evidence that the Hoxdependent control of AER-FGF expression is achieved through the regulation of key mesenchymal signals, namely Grem1 and Fgf10, ensuring proper epithelial-mesenchymal interactions. Notably, HoxA and HoxD genes contribute to both the initial activation of Grem1 and the subsequent anterior expansion of its expression domain. We propose that the intricate interactions between Hox genes and the FGF and Shh signaling pathways act as a molecular network that ensures proper limb bud growth and patterning, probably contributing to the coordination of these two processes. © 2013. Published by The Company of Biologists Ltd.
Identificadoresdoi: 10.1242/dev.089409
issn: 0950-1991
e-issn: 1477-9129
Aparece en las colecciones: (IBBTEC) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.