Specification of astrocytes by bHLH protein SCL in a restricted region of the neural tube

• Published in: Nature Vol. 438; no. 7066; pp. 360 - 363
• Main Authors: Rowitch, David H, Muroyama, Yuko, Orkin, Stuart H, Fujiwara, Yuko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 17.11.2005; Nature Publishing Group
• Subjects: Animals; Astrocytes - cytology; Astrocytes - metabolism; Basic Helix-Loop-Helix Transcription Factors - deficiency; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological and medical sciences; Cell Differentiation; Cell Lineage; Chick Embryo; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryology: invertebrates and vertebrates. Teratology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Genes; Interneurons - cytology; Interneurons - metabolism; Leukemia; Mice; Motor Neurons - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Neurology; Oligodendrocyte Transcription Factor 2; Oligodendroglia - cytology; Oligodendroglia - metabolism; Organogenesis. Fetal development; Organogenesis. Physiological fonctions; Proteins; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Spinal Cord - cytology; Spinal Cord - embryology; Spinal Cord - metabolism; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors - genetics; Transcription Factors - metabolism; Vertebrates; Helix loop helix structure; Embryo; Neuroglia; Central nervous system; Specification; Astrocyte; Cell differentiation; Vertebrata; Mammalia; Neural tube; Oligodendrocyte; Development; Transcription factor
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature04139

Astrocytes are the most abundant and functionally diverse glial population in the vertebrate central nervous system (CNS). However, the mechanisms underlying astrocyte specification are poorly understood. It is well established that cellular diversification of neurons in the embryo is generated by position-dependent extrinsic signals and combinatorial interactions of transcription factors that direct specific cell fates by suppressing alternative fates. It is unknown whether a comparable process determines embryonic astrocyte identity. Indeed, astrocyte development is generally thought to take place in a position-independent manner. Here we show multiple functions of Stem cell leukaemia (Scl, also known as Tal1), which encodes a basic helix-loop-helix (bHLH) transcription factor, in the regulation of both astrocyte versus oligodendrocyte cell fate acquisition and V2b versus V2a interneuron cell fate acquisition in the p2 domain of the developing vertebrate spinal cord. Our findings demonstrate a regionally restricted transcriptional programme necessary for astrocyte and V2b interneuron development, with striking parallels to the involvement of SCL in haematopoiesis. They further indicate that acquisition of embryonic glial subtype identity might be regulated by genetic interactions between SCL and the transcription factor Olig2 in the ventral neural tube.