How cells in the developing limb are patterned to form distal or proximal limb structures is a contentious issue. One current model - the prespecification model - proposes that cells are specified into all regions along the proximodistal axis at an early stage. Now, in contrast to these findings, Tamura and co-workers show that, while the proximal chick limb region is regionalised at an early stage of limb development, the distal region is maintained in an unregionalised condition and consists of intermingling cells (see ). These intermingling cells can adopt either a zeugopod (more proximal) or autopod(distal) fate, as shown by the analysis of HOXA11 and HOXA13 expression. Later in development, a clearer boundary can be seen between the autopod and zeugopod regions, but some cell mixing still occurs within the distal autopod region. This study redefines our understanding of cell specification within the developing limb and suggests that each limb structure is likely to be regionalised in a proximodistal direction.
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