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First published online 15 November 2006
doi: 10.1242/dev.02656

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Novel binding partners of Ldb1 are required for haematopoietic development

¹ Department of Cell Biology and Genetics, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
² Department of Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584CA, Utrecht, The Netherlands.
³ MRC Molecular Haematology Unit, The Weather all Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

^* Author for correspondence (e-mail: f.grosveld{at}erasmusmc.nl)

Accepted 22 September 2006

Ldb1, a ubiquitously expressed LIM domain binding protein, is essential in a number of tissues during development. It interacts with Gata1, Tal1, E2A and Lmo2 to form a transcription factor complex regulating late erythroid genes. We identify a number of novel Ldb1 interacting proteins in erythroleukaemic cells, in particular the repressor protein Eto-2 (and its family member Mtgr1), the cyclin-dependent kinase Cdk9, and the bridging factor Lmo4. MO-mediated knockdowns in zebrafish show these factors to be essential for definitive haematopoiesis. In accordance with the zebrafish results these factors are coexpressed in prehaematopoietic cells of the early mouse embryo, although we originally identified the complex in late erythroid cells. Based on the change in subcellullar localisation of Eto-2 we postulate that it plays a central role in the transition from the migration and expansion phase of the prehaematopoietic cells to the establishment of definitive haematopoietic stem cells.

Key words: Ldb1, Transcription factor complexes, Haematopoietic stem cells, Haematopoiesis

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