Abstract
The lower rhombic lip (LRL) is a germinal zone in the dorsal hindbrain productive of tangentially migrating neurons, streaming extramurally (mossy fiber neurons) or intramurally (climbing fiber neurons). Here we show that LRL territory, operationally defined by Wnt1 expression, is parceled into molecular subdomains predictive of cell fate. Progressing dorsoventrally, Lmx1a and Gdf7 expression identifies the primordium for hindbrain choroid plexus epithelial cells; Math1, for mossy fiber neurons; and immediately ventral to Math1 yet within Wnt1(+) territory, a climbing fiber primordium dominated by Ngn1-expressing cells. Elimination of Pax6 results in expansion of this Ngn1(+) progenitor pool and reduction in the Math1(+) pool, with accompanying later enlargement of the climbing fiber nucleus and reductions in mossy fiber nuclei. Pax6 loss also disrupts Msx expression cell-nonautonomously, suggesting Pax6 may influence LRL progenitor identity indirectly through potentiating BMP signaling. These studies suggest that underlying the diversity and proportions of fates produced by the LRL is a precise suborganization regulated by Pax6.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Afferent Pathways / cytology
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Afferent Pathways / embryology*
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Afferent Pathways / metabolism
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Body Patterning / genetics
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism
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Cell Differentiation / genetics
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Cell Movement / genetics
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Cerebellum / cytology
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Cerebellum / embryology*
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Cerebellum / metabolism
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Choroid Plexus / cytology
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Choroid Plexus / embryology
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Choroid Plexus / metabolism
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Eye Proteins / genetics
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Eye Proteins / metabolism*
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Gene Expression Regulation, Developmental / genetics
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Growth Differentiation Factors
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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LIM-Homeodomain Proteins
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Mice
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Mice, Transgenic
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Nerve Fibers / metabolism*
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Nerve Fibers / ultrastructure
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Olivary Nucleus / cytology
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Olivary Nucleus / embryology
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Olivary Nucleus / metabolism
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PAX6 Transcription Factor
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Paired Box Transcription Factors / genetics
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Paired Box Transcription Factors / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Rhombencephalon / cytology
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Rhombencephalon / embryology*
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Rhombencephalon / metabolism
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Stem Cells / cytology
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Stem Cells / metabolism*
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Transcription Factors
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Wnt1 Protein / genetics
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Wnt1 Protein / metabolism
Substances
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Atoh1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Bone Morphogenetic Proteins
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Eye Proteins
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Gdf7 protein, mouse
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Growth Differentiation Factors
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Homeodomain Proteins
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LIM-Homeodomain Proteins
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Lmx1a protein, mouse
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Nerve Tissue Proteins
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Pax6 protein, mouse
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Repressor Proteins
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Transcription Factors
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Wnt1 Protein
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Wnt1 protein, mouse
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Neurog1 protein, mouse