NPAS3 transcription factor is essential for nervous system and cranio facial development

LAURA E. GONZALEZ; LUCÍA F. FRANCHINI; ALEJANDRO CINALLI; MARCELO RUBINSTEIN; GRETEL B. KAMM

Buenos Aires

Congreso; FALAN 2016; 2016

FALAN

The gene trachealess (trh) is a member of the HLH-PAS transcription factors family and has been involved in tracheal system development in D. melanogaster. The mouse gene Neuronal PAS domain protein 3 (Npas3) has been identified as ortholog of the trh gene. Even though trh is not expressed in the developing fruitfly nervous system, it has been shown that in mouse Npas3 is widely expressed in the developing central nervous system in addition to other organs and tissues. In this work we functionally characterize the trh/NPAS3 homolog gene in zebrafish (NPAS3zf). We show that NPAS3zf is expressed all throughout development in the central nervous system, in other developing organs and in craniofacial structures. Using knockout and knockdown approaches we show that NPAS3 is important for the development of the nervous system. In addition, we found that NPAS3 is key for the development of craniofacial structures and the branchial system. We demonstrate that blockage or reduction of NPAS3 expression induces dramatic changes in sonic hedgehog (SHH) expression in the developing zebrafish larvae. Previous studies in humans had linked NPAS3 as a candidate gene for the development of holoprocencephaly. Our study reveals for the first time that vertebrate NPAS3 controls key developmental pathways involved in the development of craniofacial structures. In addition, we found that NPAS3 controls the expression of SHH, a master gene that when mutated produces holoprocencephaly.