Limb Development and Postnatal Regeneration

Hox protein function in limb skeletogenesis

We have generated knockout mice bearing mutations in Hoxa13 and Hoxd13 to examine their functions in the developing limb.  While similar in their expression patterns, the Hoxa13 and Hoxd13 mutant phenotypes are remarkably different. Indeed while Hoxa13 mutants exhibit an absence of many autopod (hand or foot) skeletal elements, Hoxd13 mutants exhibit an opposite phenotype with additional digits and an overgrowth of cartilage and bone in the joints and interdigital tissues.  From the individual mutants, one would predict that Hoxa13;Hoxd13 double mutants would be more normal as the loss of skeletal structures (Hoxa13 mutant) would be canceled out by the overgrowth of bone and skeletal tissue (Hoxd13 mutant).  Intriguingly, Hoxa13;Hoxd13 double mutants form no skeletal structures in the hand or foot a phenotype completely unpredicted by the individual mutations and one that we are keenly interested in investigating its molecular basis.

Limb Development 1

In situ hybridization analysis of Hoxa13 and Hoxd13 expression indicates nearly identical regions of expression in the developing hand and foot. 

Limb Development 2

Skeletal defects in Hoxa13 mutant limbs.  Forelimb compare A and B.  Hindlimb compare C and D.

limb development 3

Skeletal defects in Hoxd13 mutant limbs at embryonic days 14 and 16.  Note the overgrowth of tissue in the phalangeal (finger) joints in the mutant limb.

limb development 4

Absence of hand or foot skeletal element formation in the Hoxa13;Hoxd13 double mutants.