Differentiation of spermatogonial cells is a crucial part of spermatogenesis. Many of the key signalling pathways and molecules that are involved in spermatogonial differentiation have been identified, but their precise function at the cellular level as well as their downstream targets are not well understood. In this issue (p. 1502), Ming-Han Tong and colleagues address this with an in-depth look at the role of retinoic acid (RA) in spermatogonial differentiation. The authors specifically block retinoid signalling by introducing a dominant-negative mutant of RA receptor alpha (RARα) targeted to the spermatogonia of the transgenic mice. With this model, they show how a lack of RA signalling completely blocks spermatogonial differentiation in homozygous mice, which is due to the arrest of the undifferentiated cells in the G1/S phase. The authors then use RNA-Seq to probe for possible downstream targets of RA signalling in this context, and identify a role for replication-dependent core histone genes in promoting spermatogonia differentiation. These data make a significant contribution to our understanding of the mechanisms underlying spermatogonial differentiation, and the creation of a novel mouse mutant will be a valuable tool for the field.