Large scale analysis of transcription factor TTF-1/NKX2.1 target genes in GnRH secreting cell line GT1-7.

TTF-1/Nkx2.1 is a homeodomain-containing transcription factor required for the proper development of ventral forebrain, including some structures of the hypothalamus. TTF-1/Nkx2.1 remains expressed in the hypothalamus after birth and it plays a crucial role during sexual development. To identify putative TTF-1/Nkx2.1 target genes in GnRH neurons, we have studied the gene expression profile of the GT1-7 cells exogenously expressing TTF-1/Nkx2.1 coding gene. Our transcriptome analysis confirms that TTF-1/Nkx2.1 is involved in neuron morphogenesis and differentiation. Many of the newly identified TTF-1/Nkx2.1 target genes have a direct involvement with the central regulation of sexual maturity. In particular, we have identified Sparc as a gene directly regulated by TTF-1/Nkx2.1 at the promoter level. To further support the role of TTF-1 in GnRH neurons, we show that Sparc is involved in the regulation of the GnRH secretion in GT1-7 cells.