How haematopoiesis research became a fertile ground for regulatory network biology as pioneered by Eric Davidson.

Abstract

This historical perspective reviews how work of Eric H. Davidson was a catalyst and exemplar for explaining haematopoietic cell fate determination through gene regulation. Researchers studying blood and immune cells pioneered many of the early mechanistic investigations of mammalian gene regulatory processes. These efforts included the characterization of complex gene regulatory sequences exemplified by the globin and T-cell/B-cell receptor gene loci, as well as the identification of many key regulatory transcription factors through the fine mapping of chromosome translocation breakpoints in leukaemia patients. As the repertoire of known regulators expanded, assembly into gene regulatory network models became increasingly important, not only to account for the truism that regulatory genes do not function in isolation but also to devise new ways of extracting biologically meaningful insights from even more complex information. Here we explore how Eric H. Davidson's pioneering studies of gene regulatory network control in nonvertebrate model organisms have had an important and lasting impact on research into blood and immune cell development. The intellectual framework developed by Davidson continues to contribute to haematopoietic research, and his insistence on demonstrating logic and causality still challenges the frontier of research today.