Title:
Role of physical elements to regulate cellular behaviors and cell-fates in the developing brain

Yoichi Kosodo
Department of Anatomy, Kawasaki Medical School , Kurashiki , Japan
kosodo@med.kawasaki-m.ac.jp

Abstract:
During brain development, neural stem cells define specific niches within different cortical layers to control their cellular environment. Generally, communication to other cells or surrounding matrix by biochemical signaling pathways such as protein-protein interactions or humoral factors have been well studied. Much less studied, however, is how physical properties of the niche can influence behavior, growth, and differentiation of cells. My previous work revealing the role of a physical crowding effect on interkinetic nuclear migration, an oscillation of nuclear positions of neural progenitors associated with the cell-cycle (Kosodo et al, 2011; Kosodo, 2012), led us to investigate the intimate physical interactions between cells and the surrounding tissue. Among physical properties, elasticity of the matrix has been shown to have direct effects on fate determination in certain cell types in vitro . While some studies indicate that elasticity may influence the fate of cultured neural stem cells by unknown mechanisms, no evidence exists on whether this principle holds true during the physiological development of the mammalian brain. Using the developing brain as a model system, we have started clarifying roles of tissue elasticity for determining cell fates of neural cells via mechanosignaling pathways. This research aims to establish a novel concept for mammalian neurogenesis and brain development, and the outcomes will likely influence the fields of stem cell and developmental biology by clarifying unknown mechanosignaling mechanisms of somatic stem cells.

References:
Kosodo Y . Interkinetic nuclear migration: beyond a hallmark of neurogenesis (2012) Cell Mol Lif Sci. 69: 2727-2738

Kosodo Y , Suetsugu T, Suda M, Mimori-Kiyosue Y, Toida K, Baba SA, Kimura A, and Matsuzaki F. (2011) Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain. EMBO J. 30:1690-1704