Abstract
Development of the telencephalon involves the coordinated growth of diversely patterned brain structures. Previous studies have demonstrated the importance of beta-catenin-mediated Wnt signaling in proliferation and fate determination during cerebral cortical development. We found that beta-catenin-mediated Wnt signaling critically maintained progenitor proliferation in the subcortical (pallidal) telencephalon. Targeted deletion of beta-catenin in mice severely impaired proliferation in the medial ganglionic eminence without grossly altering differentiated fate. Several lines of evidence suggest that this phenotype is primarily the result of a loss of canonical Wnt signaling. As previous studies have suggested that the ventral patterning factor Sonic Hedgehog (Shh) also stimulates dorsal telencephalic proliferation, we propose a model whereby Wnt and Shh signaling promote distinct dorsal-ventral patterning while also having broader effects on proliferation that serve to coordinate the growth of telencephalic subregions.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Age Factors
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Body Patterning / genetics
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Bromodeoxyuridine / metabolism
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Calbindins
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Cell Count / methods
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Cell Proliferation
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Cells, Cultured
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Choline O-Acetyltransferase / metabolism
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Electroporation / methods
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Embryo, Mammalian
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Gene Expression Regulation, Developmental / genetics
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Green Fluorescent Proteins / metabolism
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Intercellular Signaling Peptides and Proteins / pharmacology
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Ki-67 Antigen / metabolism
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Mice
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Mice, Transgenic
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Nerve Tissue Proteins / metabolism
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Neurogenesis / drug effects
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Neurogenesis / physiology*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Organ Culture Techniques / methods
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Proliferating Cell Nuclear Antigen / metabolism
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S100 Calcium Binding Protein G / metabolism
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Signal Transduction / physiology*
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Stem Cells / drug effects
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Stem Cells / physiology
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TCF Transcription Factors / metabolism
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Telencephalon / cytology*
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Telencephalon / physiology*
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Thyroid Nuclear Factor 1
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Transcription Factor 4
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Wnt Proteins / metabolism*
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Ascl1 protein, mouse
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors
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CTNNB1 protein, mouse
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Calbindins
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Dkk1 protein, mouse
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Intercellular Signaling Peptides and Proteins
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Ki-67 Antigen
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Nerve Tissue Proteins
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Nuclear Proteins
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Proliferating Cell Nuclear Antigen
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S100 Calcium Binding Protein G
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TCF Transcription Factors
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Tcf4 protein, mouse
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Thyroid Nuclear Factor 1
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Transcription Factor 4
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Transcription Factors
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Wnt Proteins
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beta Catenin
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Green Fluorescent Proteins
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Choline O-Acetyltransferase
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Bromodeoxyuridine