Distinct 5' SCL enhancers direct transcription to developing brain, spinal cord, and endothelium: neural expression is mediated by GATA factor binding sites.
The SCL gene encodes a basic helix-loop-helix transcription factor with a pivotal role in the development of endothelium and of all hematopoietic lineages. SCL is also expressed in the central nervous system, although its expression pattern has not been examined in detail and its function in neural development is unknown. In this article we present the first analysis of SCL transcriptional regulation in vivo. We have identified three spatially distinct regulatory modules, each of which was both necessary and sufficient to direct reporter gene expression in vivo to three different regions within the normal SCL expression domain, namely, developing endothelium, midbrain, and hindbrain/spinal cord. In addition we have demonstrated that GATA factor binding sites are essential for neural expression of the SCL constructs. The midbrain element was particularly powerful and axonal lacZ expression revealed the details of axonal projections, thus implicating SCL in the development of occulomotor, pupillary, or retinotectal pathways. The neural expression pattern of the SCL gene was highly conserved in mouse, chicken, and zebrafish embryos and the 5' region of the chicken SCL locus exhibited a striking degree of functional conservation in transgenic mice. These data suggest that SCL performs critical functions in neural development. The regulatory elements identified here provide important tools for analyzing these functions.
Sinclair
A M
AM
Department of Haematology, University of Cambridge, MRC Centre, Hills Road, Cambridge, CB2 2QH, United Kingdom.
Göttgens
B
B
Barton
L M
LM
Stanley
M L
ML
Pardanaud
L
L
Klaine
M
M
Gering
M
M
Bahn
S
S
Sanchez
M
M
Bench
A J
AJ
Fordham
J L
JL
Bockamp
E
E
Green
A R
AR
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004727:Endothelium / Q000196:embryology* / Q000378:metabolism; D017930:Genes, Reporter; D017403:In Situ Hybridization; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D011518:Proto-Oncogene Proteins; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014018:Tissue Distribution; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D029961:Zebrafish Proteins; C489366:Tal1 protein, mouse; C489367:tal1 protein, zebrafish