This article fails to reference and take into account a key report by Chatzi et al. 2011 (PLoS Biology; doi:10.1371/journal.pbio.1000609; Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia) that undercuts the assumption made by the authors that forebrain cortical expansion actually requires retinoic acid (RA) signaling. The main point the authors make here is that CoupTFI interacts with RA signaling to control embryonic forebrain cortical expansion, a conclusion that depends upon the studies previously reported by this group and referenced here (Siegenthaler et al. 2009, Cell) where they suggested that RA generated in the meninges by RDH10 (that converts retinol to retinaldehyde) and RALDH2 (that converts retinaldehyde to RA) diffuses into the forebrain and stimulates asymmetric cell division in the cortex; in the Cell paper they employed a mouse ENU Rdh10 mutant that reduces but does not eliminate meningeal RA synthesis in E14.5 embryos. However, the view that RA is a critical inducer of cortical neurogenesis has been challenged by Chatzi et al. 2011 (PLoS Biology) who generated E14.5 Raldh2 knockout mouse embryos that completely lack forebrain RA activity in the meninges and cortex. Chatzi et al. 2011 (PLoS Biology) suggested that the forebrain defect in Rdh10 mutants may be secondary to a defect in craniofacial morphology leading to a distorted cranium that effects cortical morphology rather than RA controlling cortical divisions directly in the forebrain. This conclusion is consistent with other studies showing that Rdh10 mutants completely lack RA activity in the cranial neural crest at E9.5 (RDH10 is the only source of retinaldehyde for craniofacial tissues), whereas Raldh2 mutants maintain RA synthesis in craniofacial tissues due to the presence of RALDH3 that is redundant with RALDH2 in catalyzing the last step in RA synthesis, explaining why Raldh2 mutants do not exhibit a distorted cranium. Thus, the conclusions in this PLoS ONE article concerning CoupTFI need to be viewed from the perspective that RA does not act in the forebrain cortex. A more reasonable conclusion may be that CoupTF1 acts independent of RA signaling in the forebrain cortex. Indeed, the evidence that RA and CoupTFI interact in other systems (as indicated by the authors in their Abstract) is scant at best, and may be an artifact of those previous studies (referenced in the Introduction) which are based upon the observation that CoupTFI and RA receptors bind similar response elements.