Abstract
The hypothalamus is a region of the diencephalon with particularly complex patterning. Sonic hedgehog (Shh), encoding a protein with key developmental roles, shows a peculiar and dynamic diencephalic expression pattern. Here, we use transgenic strategies and in vitro experiments to test the hypothesis that Shh expressed in the diencephalic neuroepithelium (neural Shh) coordinates tissue growth and patterning in the hypothalamus. Our results show that neural Shh coordinates anteroposterior and dorsoventral patterning in the hypothalamus and in the diencephalon-telencephalon junction. Neural Shh also coordinates mediolateral hypothalamic patterning, since it is necessary for the lateral hypothalamus to attain proper size and is required for the specification of hypocretin/orexin cells. Finally, neural Shh is necessary to maintain expression of differentiation markers including survival factor Foxb1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Analysis of Variance
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Animals
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Apoptosis / genetics
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Apoptosis / physiology
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Body Patterning / genetics
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Body Patterning / physiology*
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Bromodeoxyuridine / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / physiology
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Cell Proliferation
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Embryo, Mammalian
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Exons / genetics
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Forkhead Transcription Factors / genetics
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Gene Expression Regulation, Developmental / physiology*
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Green Fluorescent Proteins / genetics
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Hedgehog Proteins / genetics
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Hedgehog Proteins / metabolism*
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Hypothalamus / cytology*
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Hypothalamus / embryology
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In Situ Nick-End Labeling / methods
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In Vitro Techniques
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Mice
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Mice, Transgenic
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Mutation / genetics
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neural Pathways / embryology
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Neuroepithelial Cells / physiology*
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Signal Transduction / genetics
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Signal Transduction / physiology*
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beta-Galactosidase / genetics
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beta-Galactosidase / metabolism
Substances
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Forkhead Transcription Factors
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Foxb1 protein, mouse
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Hedgehog Proteins
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Nerve Tissue Proteins
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Shh protein, mouse
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Green Fluorescent Proteins
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beta-Galactosidase
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Bromodeoxyuridine