LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development
2018
During
limb development, fibroblast growth factors (Fgfs) govern proximal–distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal–distal and anterior–posterior axes by maintaining
Sonic hedgehog(Shh) expression in cells of the
zoneof
polarizing activity(ZPA) in the distal posterior mesoderm. Shh, in turn, maintains Fgfs in the
apical ectodermal ridge(AER) that caps the distal tip of the
limb bud. Crosstalk between Fgf and Shh signaling is critical for patterned
limb development, but the mechanisms underlying this feedback loop are not well-characterized. Implantation of Fgf beads in the proximal posterior
limb budcan maintain SHH expression in the former ZPA domain (evident 3 h after application), while prolonged exposure (24 h) can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations accentuated genes involved in SHH regulation. Comparative analysis identified 25 candidates common to both treatments, with eight linked to SHH expression or function. Furthermore, we demonstrated that LHX2, a LIM Homeodomain transcription factor, is an intermediate in the FGF-mediated regulation of SHH. Our data suggest that LHX2 acts as a competency factor maintaining distal posterior SHH expression
subjacentto the AER.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
81
References
5
Citations
NaN
KQI