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dc.contributor.authorSeong-Kyu, Choe
dc.contributor.authorVlachakis, Nikolaos
dc.contributor.authorSagerstrom, Charles G.
dc.date2022-08-11T08:08:56.000
dc.date.accessioned2022-08-23T16:13:07Z
dc.date.available2022-08-23T16:13:07Z
dc.date.issued2002-02-07
dc.date.submitted2008-08-26
dc.identifier.citationDevelopment. 2002 Feb;129(3):585-95.
dc.identifier.issn0950-1991 (Print)
dc.identifier.pmid11830560
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33545
dc.description.abstractMeis homeodomain proteins function as Hox-cofactors by binding Pbx and Hox proteins to form multimeric complexes that control transcription of genes involved in development and differentiation. It is not known what role Meis proteins play in these complexes, nor is it clear which Hox functions require Meis proteins in vivo. We now show that a divergent Meis family member, Prep1, acts as a Hox co-factor in zebrafish. This suggests that all Meis family members have at least one shared function and that this function must be carried out by a conserved domain. We proceed to show that the Meinox domain, an N-terminal conserved domain shown to mediate Pbx binding, is sufficient to provide Meis activity to a Pbx/Hox complex. We find that this activity is separable from Pbx binding and resides within the M1 subdomain. This finding also presents a rational strategy for interfering with Meis activity in vivo. We accomplish this by expressing the Pbx4/Lzr N-terminus, which sequesters Meis proteins in the cytoplasm away from the nuclear transcription complexes. Sequestering Meis proteins in the cytoplasm leads to extensive loss of rhombomere (r) 3- and r4-specific gene expression, as well as defective rhombomere boundary formation in this region. These changes in gene expression correlate with impaired neuronal differentiation in r3 and r4, e.g. the loss of r3-specific nV branchiomotor neurons and r4-specific Mauthner neurons. We conclude that Meis family proteins are essential for the specification of r3 and r4 of the hindbrain.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11830560&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dev.biologists.org/content/129/3/585.long
dc.subjectAmino Acid Sequence; Animals; Cell Differentiation; Conserved Sequence; DNA-Binding Proteins; Homeodomain Proteins; Nerve Tissue Proteins; Neurons; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins; Rhombencephalon; Transcription Factors; Zebrafish; Zebrafish Proteins
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleMeis family proteins are required for hindbrain development in the zebrafish
dc.typeJournal Article
dc.source.journaltitleDevelopment (Cambridge, England)
dc.source.volume129
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/217
dc.identifier.contextkey604109
html.description.abstract<p>Meis homeodomain proteins function as Hox-cofactors by binding Pbx and Hox proteins to form multimeric complexes that control transcription of genes involved in development and differentiation. It is not known what role Meis proteins play in these complexes, nor is it clear which Hox functions require Meis proteins in vivo. We now show that a divergent Meis family member, Prep1, acts as a Hox co-factor in zebrafish. This suggests that all Meis family members have at least one shared function and that this function must be carried out by a conserved domain. We proceed to show that the Meinox domain, an N-terminal conserved domain shown to mediate Pbx binding, is sufficient to provide Meis activity to a Pbx/Hox complex. We find that this activity is separable from Pbx binding and resides within the M1 subdomain. This finding also presents a rational strategy for interfering with Meis activity in vivo. We accomplish this by expressing the Pbx4/Lzr N-terminus, which sequesters Meis proteins in the cytoplasm away from the nuclear transcription complexes. Sequestering Meis proteins in the cytoplasm leads to extensive loss of rhombomere (r) 3- and r4-specific gene expression, as well as defective rhombomere boundary formation in this region. These changes in gene expression correlate with impaired neuronal differentiation in r3 and r4, e.g. the loss of r3-specific nV branchiomotor neurons and r4-specific Mauthner neurons. We conclude that Meis family proteins are essential for the specification of r3 and r4 of the hindbrain.</p>
dc.identifier.submissionpathgsbs_sp/217
dc.contributor.departmentBiochemistry and Molecular Pharmacology
dc.contributor.departmentMorningside Graduate School of Biomedical Sciences
dc.source.pages585-95
dc.contributor.studentNikolaos Vlachakis


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