THE TRACHEALESS HOMOLOG NPAS3 IS CRITICAL FOR NERVOUS SYSTEM AND CRANIOFACIAL DEVELOPMENT IN ZEBRAFISH

LAURA GONZALEZ; LUCIA FLORENCIA FRANCHINI; ALEJANDRO RAUL CINALLI; GRETEL BETIANA KAMM

Medellín

Congreso; IX Latin American Society for Developmental Biology Meeting 2017; 2017

Latin American Society for Developmental Biology

The gene trachealess (trh) is a member of the bHLH-PAS transcriptionfactors family and has been involved in tracheal system developmentin D. melanogaster . The mouse gene Neuronal PAS Domain Protein3 (NPAS3) has been identified as ortholog of the trh gene. Eventhough trh is not expressed in the developing fruitfly nervous system,it has been shown that in mouse NPAS3 is widely expressed in thedeveloping central nervous system in addition to other organs andtissues. In this work we functionally characterize the trh/NPAS3homolog gene in zebrafish ( NPAS3ZF ). We show that NPAS3ZF isexpressed all throughout development in the central nervous system,in other developing organs and in craniofacial structures. Usingknockout and knockdown approaches we show that NPAS3 isimportant for the development of the nervous system. In addition, wefound that NPAS3 is key for the development of craniofacialstructures and the branchial system. We demonstrate that blockageor reduction of NPAS3 expression induces dramatic changes in Sonichedgehog (Shh) expression in the developing zebrafish larvae.Previous studies in humans had linked NPAS3 as a candidate gene forthe development of Holoprocencephaly. Our study reveals for thefirst time that vertebrate NPAS3 controls key developmentalpathways involved in the development of craniofacial structures. Inaddition, we found that NPAS3 controls the expression of Shh , amaster gene that when mutated produces Holoprocencephaly.