The Evolutionary Origins of Vertebrate Haematopoiesis: Insights from Non-Vertebrate Chordates

Abstract

Both vertebrates and non-vertebrates have haematopoietic systems; however the vertebrate system appears to produce a greater diversity of blood cell types. Erythrocyte and lymphocytes may be examples of vertebrate-specific novelties. To understand how they evolved, the haematopoietic gene regulatory network of the vertebrate ancestor must be inferred from studying extant organisms. In this thesis gene expression analysis was used to identify which non-vertebrate chordate species is the best candidate to represent the vertebrate ancestor. Homologues of ikaros, a transcription factor involved in vertebrate haematopoiesis, were expressed in the developmental precursors of haemocytes in ascidian embryos and what appear to be primordial germ cells in amphioxus embryos. Reanalysis of publicly available transcriptome data suggest that homologues of a number of genes expressed in vertebrate haematopoietic cells or blood cells were expressed in ascidian haemocytes. These data indicate that ascidians represent the better candidate organism. In addition, the evolution of the transcription factors gata1, gata2 and gata3 was investigated. gata1 plays critical roles in the development of erythrocytes, a lineage which appears to be absent from non-vertebrate chordates. Knockdown and rescue experiments revealed that amphioxus gata1/2/3 and zebrafish gata1 are functionally equivalent in erythrocyte development. This highlights the importance of cis-regulatory changes in the evolution of gata1 and erythrocytes. A 934bp regulatory region of ascidian gata1/2/3 did not produce expression in zebrafish haematopoietic cells. However, now that the method has been successfully established, it could be used to investigate a number of questions related to the evolution of vertebrate haematopoiesis.

Date of Award	1 Aug 2015
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Christopher Thompson (Supervisor) & Toki Takahashi (Supervisor)