The Activity of LHx2‐Associated cis Regulatory Modules

Abstract

Limb outgrowth is controlled, in part, by fibroblast growth factor (FGF) and sonic hedgehog (Shh). FGF up‐regulation of SHH is essential for coordinated limb pattering; however, not much is known about this mechanism. We recently found that LHX2 is an intermediate in FGF‐mediated SHH up‐regulation. LHX2 is part of a family of genes that are known to integrate signaling events. Thus, we hypothesized that FGF would up‐regulate LHX2 through associated potential cis regulatory modules (PCRM). Multiple PCRMs were found in association with the LHX2 locus. PCRMs were screened using comparative genomics, proximity to the LHX2 promoter, and transcription factor binding sites related to FGF signaling. To exam the role of suspected PCRMs, we electroporated PCRM‐reporter constructs into chick embryos. We found one PCRM with activity in the brain coincident with LHX2 expression, but none of our initial PCRMs exhibited activity in the limbs. We reevaluated the LHX2‐associated PCRMs in light of limb‐specific chromatin activation marks and identified 5 additional PCRMs for analysis. Studies are underway to determine limb‐related PCRM activity of this new cohort. Investigations regarding the relationship between FGF and LHX2 will provide important insights into the mechanisms underlying the FGF‐SHH regulatory loop.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.