Research in the LaBonne laboratory was the first to link Myc to the acquisition of stem cell attributes, and demonstrated that Myc plays a central role in neural crest ontogeny, several years prior to the initial report of the Yamanaka factors. This work proposed that Myc plays this key role in many stem cell populations, and more recent work by others has shown this to be the case. LaBonne’s group subsequently demonstrated that Id3 was a key Myc target in maintaining neural crest potency. The growing realization of the commonalities between pluripotent blastula inner cell mass cells/embryonic stem cells and neural crest cells led LaBonne’s group to proposed a new model in which neural crest cells arose via retention of the regulatory network controlling pluripotency in blastula cells and showed that neural crest cells possess a previously unrecognized capacity to form endoderm. This pioneering work created a new framework for studying these developmentally and clinically important cells. The LaBonne lab also demonstrated a role for FGF signaling in the retention of pluripotency underling neural crest genesis, and discovered that a novel switching of effector pathways, from Map Kinase to PI3 Kinase, controls the transit from pluripotency to lineage restriction. Recent work in the LaBonne lab has focused on the epigenetic control of pluripotency in naïve blastula cells, including a central role for HDAC activity in both maintaining blastula pluripotentcy and establishment of the neural crest stem cell population.