Hox9 Sets the Stage

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Science  18 Mar 2011:
Vol. 331, Issue 6023, pp. 1366
DOI: 10.1126/science.331.6023.1366-b
CREDIT: XU AND WELLIK, PROC. NATL. ACAD. SCI. U.S.A. 108, 10.1073/PNAS.1018161108 (2011)

An intricate interplay of signaling pathways, which include polarized gradients of Hand2 and Gli3 expression and subsequent Sonic hedgehog signaling, is important early on in anterior-posterior patterning in limb development. How these signaling gradients are established, however, is unknown. Xu and Wellik use mouse genetics to examine whether Hox9 genes, which are expressed along the forelimb anterior-posterior axis, play a role in early mouse limb development. No obvious defects are seen in mice with single mutations of the Hox9 genes (Hoxa9, Hoxb9, Hoxc9, and Hoxd9); however, mutation of all four Hox9 genes resulted in severe forelimb defects, with total loss of the posterior skeletal elements. This phenotype resembles the forelimb phenotype of Shh and Hand2 mutants. Subsequent analysis of in situ mRNA expression revealed that the Hox9 genes act upstream of Hand2 to initiate the posterior limb compartment and Hand2 polarity, which in turn initiates Shh signaling. No defects in hindlimb development were observed in Hox9 mutant mice, which suggested that the role of Hox9 genes in setting up limb polarity is restricted to forelimb development only.

Proc. Natl. Acad. Sci. U.S.A. 108, 10.1073/pnas.1018161108 (2011).

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