A long non-coding RNA mediates the hormone responsiveness of during male urogenital development.

The novel long non-coding RNA (lncRNA) is extraordinarily conserved in both its location (syntenic with an essential gene in anogenital patterning) and sequence. Here we show that is upregulated following the testosterone surge from the developing testis and directly interacts with positively regulating its expression. expression is suppressed by estrogen, which in turn suppresses the expression of . Moreover, the loss of leads to reduced resulting in a severe hypospadias phenotype. The human gene is also co-expressed with in the developing human penis suggesting a conserved function for this gene in urethral closure. Together our data identify as a novel molecular regulator of urethral closure and implicate it as a target of endocrine disruption in the etiology of hypospadias.