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Members of the bHLH-PAS family regulate Shh transcription in forebrain regions of the mouse CNS
- Source :
- Development. 127:4701-4709
- Publication Year :
- 2000
- Publisher :
- The Company of Biologists, 2000.
-
Abstract
- The secreted protein sonic hedgehog (Shh) is required to establish patterns of cellular growth and differentiation within ventral regions of the developing CNS. The expression of Shh in the two tissue sources responsible for this activity, the axial mesoderm and the ventral midline of the neural tube, is regulated along the anteroposterior neuraxis. Separate cis-acting regulatory sequences have been identified which direct Shh expression to distinct regions of the neural tube, supporting the view that multiple genes are involved in activating Shh transcription along the length of the CNS. We show here that the activity of one Shh enhancer, which directs reporter expression to portions of the ventral midbrain and diencephalon, overlaps both temporally and spatially with the expression of Sim2. Sim2 encodes a basic helix-loop-helix (bHLH-PAS) PAS domain containing transcriptional regulator whose Drosophila homolog, single-minded, is a master regulator of ventral midline development. Both vertebrate and invertebrate Sim family members were found sufficient for the activation of the Shh reporter as well as endogenous Shh mRNA. Although Shh expression is maintained in Sim2−/− embryos, it was determined to be absent from the rostral midbrain and caudal diencephalon of embryos carrying a dominant-negative transgene that disrupts the function of bHLH-PAS proteins. Together, these results suggest that bHLH-PAS family members are required for the regulation of Shh transcription within aspects of the ventral midbrain and diencephalon.
- Subjects :
- animal structures
Transcription, Genetic
Mice, Transgenic
Biology
Midbrain
Mice
Diencephalon
Prosencephalon
Genes, Reporter
Mesencephalon
Basic Helix-Loop-Helix Transcription Factors
medicine
Animals
Hedgehog Proteins
Sonic hedgehog
Enhancer
Molecular Biology
Body Patterning
Embryonic Induction
Mice, Knockout
Genetics
Basic helix-loop-helix
Helix-Loop-Helix Motifs
Neural tube
Gene Expression Regulation, Developmental
Proteins
beta-Galactosidase
Cell biology
medicine.anatomical_structure
SIM2
embryonic structures
Forebrain
Trans-Activators
biology.protein
Transcription Factors
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Volume :
- 127
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....10268fd707c9b96f386f77c2459120c0
- Full Text :
- https://doi.org/10.1242/dev.127.21.4701