Crosstalk between nitric oxide and retinoic acid pathways is essential for amphioxus pharynx development

During animal ontogenesis, body axis patterning is finely regulated by complex interactions between several signaling pathways. Nitric Oxide (NO) and Retinoic Acid (RA) are potent morphogens that play a pivotal role in vertebrate development. Their involvement in axial patterning of head and pharynx shows conserved features in the chordate phylum. Indeed, in the cephalochordate amphioxus NO and RA are crucial for the correct development of pharyngeal structures. Here we demonstrate the functional cooperation between NO and RA occurring in amphioxus embryogenesis. During neurulation, NO modulates RA production through the transcriptional regulation of Aldh1a.2 that irreversibly converts retinaldehyde into RA. On the other hand, RA regulates the transcription of Nos genes, probably through RA Response Elements found in their regulatory regions. The reciprocal regulation of NO and RA pathways results to be essential for the normal pharyngeal development in amphioxus and suggests that this regulatory crosstalk could be conserved in vertebrates.