Present address: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
The essential haematopoietic transcription factor Scl is also critical for neuronal development
Article first published online: 5 APR 2006
European Journal of Neuroscience
Volume 23, Issue 7, pages 1677–1689, April 2006
How to Cite
Bradley, C. K., Takano, E. A., Hall, M. A., Göthert, J. R., Harvey, A. R., Begley, C. G. and van Eekelen, J. A. M. (2006), The essential haematopoietic transcription factor Scl is also critical for neuronal development. European Journal of Neuroscience, 23: 1677–1689. doi: 10.1111/j.1460-9568.2006.04712.x
- Issue published online: 5 APR 2006
- Article first published online: 5 APR 2006
- Received 31 July 2005, revised 5 December 2005, accepted 30 December 2005
- mouse brain;
- stem cell leukaemia;
The basic helix-loop-helix (bHLH) transcription factor Scl displays tissue-restricted expression and is critical for the establishment of the haematopoietic system; loss of Scl results in embryonic death due to absolute anaemia. Scl is also expressed in neurons of the mouse diencephalon, mesencephalon and metencephalon; however, its requirement in those sites remains to be determined. Here we report conditional deletion of Scl in neuronal precursor cells using the Cre/LoxP system. Neuronal-Scl deleted mice died prematurely, were growth retarded and exhibited an altered motor phenotype characterized by hyperactivity and circling. Moreover, ablation of Scl in the nervous system affected brain morphology with abnormal neuronal development in brain regions known to express Scl under normal circumstances; there was an almost complete absence of Scl-null neurons in the hindbrain and partial loss of Scl-null neurons in the thalamus and midbrain from early neurogenesis onwards. Our results demonstrate a crucial role for Scl in the development of Scl-expressing neurons, including γ-aminobutyric acid (GABA)ergic interneurons. Our study represents one of the first demonstrations of functional overlap of a single bHLH protein that regulates neural and haematopoietic cell development. This finding underlines Scl's critical function in cell fate determination of mesodermal as well as neuroectodermal tissues.