Identification of genes controlled by LMX1B in the developing mouse limb bud

In the developing limb, dorsal-ventral patterning is controlled by the transcription factor LMX1B, expressed in the dorsal mesenchyme. Loss of Lmx1b function in mice or humans results in the loss of dorsal limb structures and Nail-Patella syndrome, but the effectors through which LMX1B controls limb patterning are virtually unknown. Using microarrays to analyze the differential expression of mRNAs in wild-type vs. Lmx1b(-/-) limb buds, we have identified hundreds of genes as putative LMX1B targets. Analysis of a subset of these candidates by in situ mRNA localization has identified eight genes previously unknown to require Lmx1b for their dorsal-ventral restriction of expression in the limb. Furthermore, our results suggest that LMX1B controls different targets along the proximal-distal axis of the limb, and suggest the existence of a dorsal proximal limb region that is rich in mRNAs requiring Lmx1b for their expression.