Temporally restricted substrate interactions direct fate and specification of neural precursors derived from embryonic stem cells

Abstract

It was, until now, not entirely clear how the nervous system attains its cellular phenotypic diversity and wired complexity during development. Here we describe how environmental interactions alone can modify the development of neurogenic precursor cells. Upon evaluating distinct growth-permissive substrates in an embryonic stem cell-neurogenesis assay, we found that laminin, fibronectin, and gelatin instruct neural fate and alter the functional specification of neurons when applied at distinct stages of development. Changes in phenotypic, electrophysiological, and molecular characteristics could resemble cellular events and interactions in the early embryonic brain and may explain why these extracellular matrix components transiently demarcate certain developing brain structures.