Hmx gene conservation identifies the evolutionary origin of vertebrate cranial ganglia

Abstract

The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia (CSG) which develop from cranial placodes; however understanding the evolutionary origin of placodes and CSGs is hampered by the gulf between living lineages and difficulty in assigning homology between cell types and structures. Here we use the Hmx gene family to address this question. We show Hmx is a constitutive component of vertebrate CSG development and that Hmx in the tunicate Ciona is able to drive the differentiation program of Bipolar Tail Neurons (BTNs), cells previously thought neural crest homologs. Using Ciona and lamprey transgenesis we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx in the stem-vertebrate lineage. Strikingly, we also show robust vertebrate Hmx enhancer function in Ciona, demonstrating that deep conservation of the upstream regulatory network spans the evolutionary origin of vertebrates. These experiments demonstrate regulatory and functional conservation between Ciona and vertebrate Hmx, and confirm BTNs as CSG homologs. Our analysis also identifies derived evolutionary changes, including a genetic basis for secondary simplicity in Ciona and unique regulatory complexity in vertebrates.