Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a newhairy/E(spl)gene pair
doi: 10.1242/dev.01525
pmid: 15590746
Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a newhairy/E(spl)gene pair
The intervening zone (IZ) is a pool of progenitor cells located at the midbrain-hindbrain boundary (MHB) and important for MHB maintenance,midbrain-hindbrain growth and the generation of midbrain-hindbrain neurons. Recently, we implicated the Hairy/E(spl) transcription factor Her5 in the formation of the medial (most basal) part of the IZ (MIZ) in zebrafish; the molecular bases for lateral IZ (LIZ) formation, however, remain unknown. We now demonstrate that her5 is physically linked to a new family member, him, displaying an identical MHB expression pattern. Using single and double knockdowns of him and her5, as well as a him+her5 deletion mutant background (b404), we demonstrate that Him and Her5 are equally necessary for MIZ formation, and that they act redundantly in LIZ formation in vivo. We show that these processes do not involve cross-regulation between Him and Her5 expression or activities,although Him and Her5 can heterodimerize with high affinity. Increasing the function of one factor when the other is depleted further shows that Him and Her5 are functionally interchangeable. Together, our results demonstrate that patterning and neurogenesis are integrated by the her5-himgene pair to maintain a progenitor pool at the embryonic MHB. We propose a molecular mechanism for this process where the global `Him+Her5' activity inhibits ngn1 expression in a dose-dependent manner and through different sensitivity thresholds along the medio-lateral axis of the neural plate.
- Technical University of Munich Germany
- Vanderbilt University United States
Neurons, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Western, Molecular Sequence Data, Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Immunohistochemistry, Mesencephalon, Basic Helix-Loop-Helix Transcription Factors, Animals, Immunoprecipitation, RNA, Amino Acid Sequence, RNA, Messenger, Cloning, Molecular, In Situ Hybridization, Phylogeny, Body Patterning, DNA Primers, Protein Binding
Neurons, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Western, Molecular Sequence Data, Gene Expression Regulation, Developmental, Nerve Tissue Proteins, Immunohistochemistry, Mesencephalon, Basic Helix-Loop-Helix Transcription Factors, Animals, Immunoprecipitation, RNA, Amino Acid Sequence, RNA, Messenger, Cloning, Molecular, In Situ Hybridization, Phylogeny, Body Patterning, DNA Primers, Protein Binding
21 Research products, page 1 of 3
- 2013IsAmongTopNSimilarDocuments
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).52 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
