The distinction between sexes is one of the most obvious examples of morphological dimorphism in the animal kingdom. While there has been extensive research into the differentiation of the ovaries and testes, there is much to learn about the urogenital ridge, a bipotential tissue that makes this all possible. The LIM-homeobox gene, Lhx9 is a transcription factor critical for the formation of the urogenital ridge. We aimed to characterize the regulation of Lhx9 in the developing gonad and to investigate it’s role in oocyte maturation and fertility.
In order to investigate Lhx9 function, we used chromatin immunoprecipitation sequencing (ChIP-seq) to identify Lhx9 target genes. To investigate regulation of Lhx9 gene expression by Notch signaling, we are using in situ hybridization to demonstrate overlapping expression patterns of Lhx9 and Notch pathway genes. This will be followed by analysis of Lhx9 expression after inhibition of the Notch pathway using explant cultures.
Analysis of the role of Lhx9 in oocyte quality and fertility in will be undertaken using a heterozygote mouse. Changes in gene expression of several cell-type markers will be assessed in both later stage embryonic gonad and adult gonads.
Pathway analysis of ChIP-seq results revealed Lhx9 target genes regulate processes such as sexual differentiation and cell migration. Additionally, we found that Lhx9+/- adults, while initially fertile, develop gonadal abnormalities as they age.
Lhx9 is implicated as having a vital role in developmental pathways that may be relevant to disorders of sex determination and infertility.