VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells and requires the EglN3 prolyl hydroxylase as a downstream effector. Germline mutations of these genes cause familial pheochromocytoma and other neural crest-derived tumors. Using an unbiased shRNA screen we found that the kinesin KIF1B␤ acts downstream from EglN3 and is both necessary and sufficient for neuronal apoptosis when NGF becomes limiting. KIF1B␤ maps to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors including neuroblastomas. We identified inherited loss-of-function KIF1B␤ missense mutations in neuroblastomas and pheochromocytomas and an acquired loss-of-function mutation in a medulloblastoma, arguing that KIF1B␤ is a pathogenic target of these deletions.[Keywords: Apoptosis; kinesin; neuroblastoma; pheochromocytoma; prolyl hydroxylase] Supplemental material is available at http://www.genesdev.org.

Groupers, encompassing species in the subfamily Epinephelinae, family Serranidae, are of particular economic importance in Asian aquaculture. 1 The grouper aquaculture industry has experienced a recent trend towards increased production of hybrids, due to the improved growth and disease resistance of the hybrid compared with the parent species. 1,2 The predominantly farmed hybrid is between tiger grouper (Epinephelus fuscoguttatus) females and giant grouper (Epinephelus lanceolatus) males, which we