Lmx1a and Lmx1b are examples of highly conserved LIM homeobox transcription factors with clearly established requirements for the patterning, differentiation and adult function of diverse tissues in mammals. Not surprisingly, these transcription factors are implicated in a wide variety of human pathologies, including Nail Patella Syndrome, Parkinson’s disease, renal disease and ovarian carcinoma. However, few examples exist where precise target genes, binding partners and downstream cellular functions are known. CG32105 is a Drosophila homolog of both Lmx1a and Lmx1b, and has never been studied.
Using CRISPR, we have generated flies carrying a full deletion of the CG32105 open reading frame. Surprisingly, homozygous adults are viable with no obvious defects in external morphology or behavior. However, females are sterile with collapsed ovaries. Looking as early as larval stages, we show this phenotype likely arises from a primary defect in the development of ovarian support structures. Consistent with this, lineage-tracing analysis reveals that a CG32105 putative enhancer drives expression in what is possibly a common somatic ovary progenitor. Furthermore, by driving knock down and over-expression of the transcript, we find this same enhancer is sufficient to both recapitulate and rescue the knock out phenotype, respectively. Taken together, these data argue a requirement for this Lmx1 homolog in the development of Drosophila ovary support structures, and indicate we have the tools necessary to address function at precise temporal and cell-specific levels. Using both a candidate approach and a simple, non-biased screening approach, we expect rapid and precise dissection of the mechanisms through which this Lmx1 homolog mediates Drosophila ovary development. Interestingly, while Drosophila oogenesis is a highly studied process with major contributions to cell biology, very little is known with regards to the genetic mechanisms through which the ovary develops. We therefore anticipate contributing not only to the understanding of LIM homeobox transcription factors, but also to the understanding of this largely understudied developmental process, which could be used as a powerful, genetically tractable model in developmental biology.