Abstract
Intermediate neural progenitor cells (INPs) need to avoid differentiation and cell cycle exit while maintaining restricted developmental potential, but mechanisms preventing differentiation and cell cycle exit of INPs are not well understood. In this study, we report that the Drosophila homolog of mammalian Sp8 transcription factor Buttonhead (Btd) prevents premature differentiation and cell cycle exit of INPs in Drosophila larval type II neuroblast (NB) lineages. We show that the loss of Btd leads to elimination of mature INPs due to premature differentiation of INPs into terminally dividing ganglion mother cells. We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs. We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs. Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.
Keywords:
Buttonhead; D. melanogaster; Prospero; Sp8; developmental biology; intermediate neural progenitor; neuroblast; neuroscience; pointed; stem cells.
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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Animals
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Brain / cytology
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Brain / growth & development
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Brain / metabolism*
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Cell Cycle / genetics
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Cell Differentiation
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Cell Lineage / genetics
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Drosophila Proteins / antagonists & inhibitors
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Drosophila melanogaster / cytology
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Drosophila melanogaster / genetics*
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Drosophila melanogaster / growth & development
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Drosophila melanogaster / metabolism
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Gene Expression Regulation, Developmental
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Larva / cytology
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Larva / genetics
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Larva / growth & development
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Larva / metabolism
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Mutation
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Neural Stem Cells / cytology
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Neural Stem Cells / metabolism*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription, Genetic
Substances
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DNA-Binding Proteins
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Drosophila Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Transcription Factors
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btd protein, Drosophila
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pnt protein, Drosophila
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pros protein, Drosophila