Insulin-like Growth Factor II: An Essential Adult Stem Cell Niche Constituent in Brain and Intestine

Abstract

Summary: Tissue-specific stem cells have unique properties and growth requirements, but a small set of juxtacrine and paracrine signals have been identified that are required across multiple niches. Whereas insulin-like growth factor II (IGF-II) is necessary for prenatal growth, its role in adult stem cell physiology is largely unknown. We show that loss of Igf2 in adult mice resulted in a ∼50% reduction in slowly dividing, label-retaining cells in the two regions of the brain that harbor neural stem cells. Concordantly, induced Igf2 deletion increased newly generated neurons in the olfactory bulb accompanied by hyposmia, and caused impairments in learning and memory and increased anxiety. Induced Igf2 deletion also resulted in rapid loss of stem and progenitor cells in the crypts of Lieberkühn, leading to body-weight loss and lethality and the inability to produce organoids in vitro. These data demonstrate that IGF-II is critical for multiple adult stem cell niches. : In this article, Levison, Wood and colleagues demonstrate that IGF-II expression in the adult mouse is necessary for maintaining multiple adult stem cell niches including in the subventricular and subgranular zones of the brain and in the crypts of Lieberkühn of the gut. Keywords: neural stem cell, IGF-II, intestinal stem cell, subventricular zone, subgranular zone, crypt of Lieberkühn, neurogenesis