During the development of the mouse embryo tightly regulated differentiation pathways lead to the formation of the tissues and organs of the adult animal. The role of Ldb1 during embryonic development and in particular during hematopoiesis and neural development will be the focus of this thesis. The first chapter of this thesis is a general introduction that covers the initial stages during the formation of the mouse embryo, the onset of hematopoiesis in the extra-embryonic tissues followed by the emergence of HSCs in the intra-embryonic PSp/AGM and the shift of hematopoiesis initially to the fetal liver and finally the bone marrow. In addition the chapter includes an overview of the signalling pathways and transcription factors that are involved in the regulation of hematopoiesis. Finally Ldb1 is introduced as a member of multi-protein complexes that regulate gene expression and cell differentiation and as a facilitator of long range interactions in transcription regulation. In the second chapter the phenotype of the Ldb1-/- mouse is described in detail. The deletion of Ldb1 was found to be detrimental for embryonic development as the resulting phenotype is characterized by early embryonic lethality and severe defects. Mouse expression arrays were used in order to gain insight into which development regulatory pathways and factors were misregulated in the absence of Ldb1. In the third chapter the role of Ldb1 in early hematopoietic development and the emergence of the hemangioblast was investigated in detail with the use of an Ldb1-/- ES cell line that was differentiated into embryoid bodies. Mouse expression arrays were used in order to establish which factors act downstream of Ldb1 in the regulation of hematopoiesis in the mouse embryo. In the fourth chapter the role of Ldb1 in neural development was investigated with the use of the Ldb1-/- ES cell line that was differentiated into Neural Stem Cells (NSCs). Mouse expression arrays were used to determine the position of Ldb1 in the hierarchy of factors that are involved in the emergence of the NSCs. In the fifth chapter the role of Ldb1 in cell differentiation and transcription regulation is discussed in detail and applications of the present findings into future directions are proposed.

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F.G. Grosveld (Frank)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Mylona, M.-A. (2009, June 10). The Diverse Role of Ldb1 in Cell Differentiation and Mouse Embryonic Development. Retrieved from http://hdl.handle.net/1765/16405