Stanforth, Hannah Amy; (2018) Transcriptional targets of Eph receptor and ephrin signalling in the zebrafish hindbrain. Doctoral thesis (Ph.D), UCL (University College London).

Preview

Text Stanforth_10053620_thesis.pdf Download (28MB) | Preview

Abstract

In vertebrates, there is a large family of Eph receptor tyrosine kinases and their ephrin ligands, which have complex and varied roles during development and in adult homeostasis. The most researched role of Eph receptors and ephrins is in control of cell migration through the regulation of the actin cytoskeleton and cell adhesion. More recently, it has been found that in some tissues Eph-ephrin signalling also leads to changes in gene transcription, for example to control cell differentiation. In the zebrafish hindbrain, Eph receptors and ephrins are expressed segmentally in the rhombomeres in a complementary pattern with respect to their binding partner. Signalling via this pathway induces a unique cell population to arise at rhombomere borders, known as the boundary cells. In order to understand more about Eph receptor and ephrin function in the hindbrain, RNA-sequencing was carried out on dissected hindbrains of zebrafish with endogenous Eph-ephrin signalling and fish that lack Eph-ephrin signalling. The transcriptional profiles were then compared to identify potential downstream targets, which were verified using RT-qPCR and in situ hybridisation. This identified four genes regulated downstream of Eph-ephrin signalling that are markers of progenitor cells and neural differentiation. When Eph-ephrin signalling is disrupted the expression of these genes alters, and the expression pattern of one gene, mdka, was consistent with loss of hindbrain boundary cells. To investigate this observation further, the expression of progenitor and neurogenic markers was determined when Eph-ephrin signalling was disrupted. This supported previous studies which found that Eph-ephrin signalling is required for formation of boundary cells and that boundary cell loss results in ectopic neurogenesis. In addition, it was found that ectopic neurogenesis was accompanied by the depletion of nestin-expressing neural progenitor cells at later stages of development. Together these findings support previous work showing that hindbrain boundary cells are essential for restricting neurogenesis to neurogenic zones adjacent to the boundaries.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as XMLJSONCSV

Archive Staff Only

View Item