LAUSR

Development of the embryonic head is determined by the activity of gene regulatory networks (GRN) driven by transcription factors such as LHX1 and OTX2. Analysis of genetic mutants has revealed that loss of Lhx1 function at sequential steps of embryonic head formation leads to the truncation of head structures. We have implemented Lhx1-expressing embryonic stem cells (ESCs) to generate embryos for the identification of the in vivo ensemble of LHX1 downstream target genes. We have generated embryos from ESCs harbouring a conditional Lhx1 transgene and have confirmed inducible activation of Lhx1 in the embryos that are rendered amenable for RNA-seq and ChIP-seq analyses. Meta-analysis of gene expression profiles of differentiating Lhx1-expressing ESCs and the anterior germ layers of mouse gastrula-staged embryos, and ChIPseq data on the transcriptional targets of the LHX1 orthologue in Xenopus embryos has revealed a Head GRN, consisting of 92 genes as putative targets of LHX1 in the mouse. Among the putative targets, the functional attribute of nine that have no known phenotype are being studied by analysis of the chimeras derived from genome-edited ESCs. Preliminary findings of these studies will be presented.