NFIA and GATA3, critical regulators of embryonic articular cartilage differentiation

During appendicular skeletal development, the bi-potential cartilage anlagen gives rise to transient cartilage, which is eventually replaced by bone, and articular cartilage which caps the ends of individual skeletal elements. While the molecular mechanism that regulates transient cartilage differentiation is relatively better understood, the mechanism of articular cartilage differentiation has only begun to be unraveled. Further, the molecules that coordinate articular and transient cartilage differentiation processes are very poorly understood. Here, we have characterized the regulatory roles of two transcription factors, NFIA and GATA3 in articular cartilage differentiation, maintenance and the coordinated differentiation of articular and transient cartilage. Both NFIA and GATA3 block hypertrophic differentiation. Our results suggest that NFIA is not sufficient but necessary for articular cartilage differentiation. On the other hand, while ectopic activation of GATA3 promotes articular cartilage differentiation, inhibition of GATA3 activity promotes transient cartilage differentiation at the expense of articular cartilage. Finally, we propose a novel transcriptional circuitry involved in embryonic articular cartilage differentiation, maintenance and its cross-talk with transient cartilage differentiation program.