A genome-wide screen identifies PAPP-AA-mediated IGFR signaling as a novel regulator of habituation learning.

ABSTRACT: Habituation represents a fundamental form of learning, yet the underlying molecular genetic mechanisms are not well defined. Here we report on a genome-wide genetic screen, coupled with whole-genome sequencing, that identified 14 zebrafish startle habituation mutants including mutants of the vertebrate-specific gene pregnancy-associated plasma protein-aa (pappaa). PAPP-AA encodes an extracellular metalloprotease known to increase IGF bioavailability, thereby enhancing IGF receptor signaling. We find that pappaa is expressed by startle circuit neurons, and expression of wild-type but not a metalloprotease-inactive version of pappaa restores habituation in pappaa mutants. Furthermore, acutely inhibiting IGF1R function in wild-type reduces habituation, while activation of IGF1R downstream eff

SUBMITTER: Wolman MA 

PROVIDER: S-EPMC4368495 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature