The C. elegans histone deacetylase HDA-1 is required for cell migration and axon pathfinding

Zinovyeva, Anna Y.; Graham, Serena M.; Cloud, Veronica; Forrester, Wayne C.

doi:10.1016/j.ydbio.2005.10.033

Cited by 17 publications

(17 citation statements)

References 48 publications

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“…In the vulva, hda-1 knockdown has been shown to cause a weak Muv phenotype in combination with mutations in any one of the class A and class B SynMuv genes (Lu and Horvitz 1998; Solari and Ahringer 2000). Subsequently, a similar phenotype was reported in hda-1 mutants alone (Dufourcq et al 2002; Zinovyeva et al 2006), although the SynMuv interaction was not observed (Dufourcq et al 2002). In addition, vulval cells in hda-1 animals fail to migrate and form ectopic invaginations (Dufourcq et al 2002).…”

supporting

confidence: 69%

“…HDA-1 (HDAC1), a catalytic subunit of NURD, is required for embryogenesis, gonadogenesis, germ cell formation, neuronal axon guidance, and vulval development (Dufourcq et al 2002; Zinovyeva et al 2006). In the vulva, hda-1 knockdown has been shown to cause a weak Muv phenotype in combination with mutations in any one of the class A and class B SynMuv genes (Lu and Horvitz 1998; Solari and Ahringer 2000).…”

mentioning

confidence: 99%

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Caenorhabditis elegansHistone Deacetylasehda-1Is Required for Morphogenesis of the Vulva and LIN-12/Notch-Mediated Specification of Uterine Cell Fates

Ranawade

Cumbo

Gupta

2013

G3 Genes|Genomes|Genetics

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Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1, a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-seam cell). We characterized the vulval defects by using cell fate-specific markers and found that hda-1 is necessary for the specification of all seven vulval cell types. The analysis of the vulval-uterine connection defect revealed that hda-1 is required for the differentiation of the gonadal anchor cell (AC), which in turn induces ventral uterine granddaughters to adopt π fates, leading to the formation of the uterine-seam cell. Consistent with these results, hda-1 is expressed in the vulva and AC. A search for hda-1 target genes revealed that fos-1 (fos proto-oncogene family) acts downstream of hda-1 in vulval cells, whereas egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless homolog, NHR family) mediate hda-1 function in the AC. Furthermore, we showed that AC expression of hda-1 plays a crucial role in the regulation of the lin-12/Notch ligand lag-2 to specify π cell fates. These results demonstrate the pivotal role of hda-1 in the formation of the vulva and the vulval-uterine connection. Given that hda-1 homologs are conserved across the phyla, our findings are likely to provide a better understanding of HDAC1 function in development and disease.

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supporting

confidence: 69%

mentioning

confidence: 99%

Caenorhabditis elegansHistone Deacetylasehda-1Is Required for Morphogenesis of the Vulva and LIN-12/Notch-Mediated Specification of Uterine Cell Fates

Ranawade

Cumbo

Gupta

2013

G3 Genes|Genomes|Genetics

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“…As the cortex develops, all newly generated neurons migrate past the older neurons to populate the cortical plate just below the marginal zone in a classical inside-out pattern (16). Given the known roles of HDAC1 and HDAC2 in regulating cell cycle and migration (17)(18)(19), it is interesting to see loss of HDAC1 and HDAC2 not overtly affecting migration. Mutant migrating neurons along radial glial fibers showed a moderate displacement compared with wild-type controls, however, the most pronounced phenotype was the overall lack of mature neurons after deletion of HDAC1 and HDAC2, espe- cially those born at E14.5.…”

Section: Discussionmentioning

confidence: 99%

“…Because HDACs are involved in regulation of the cell cycle (17) and have been shown to control cell migration (18,19), we speculated that the observed phenotypes could be because of inefficient neuronal migration and/or defective progenitor specification. Development of the cerebral cortex is an intricate process that involves sequential neurogenesis and migration.…”

Section: Neuronal Migration Is Intact In Cns Deletion Of Hdac1 and Hdmentioning

confidence: 99%

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Montgomery¹,

Hsieh²,

Barbosa³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

277

254

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The molecular mechanism by which neural progenitor cells commit to a specified lineage of the central nervous system remains unknown. We show that HDAC1 and HDAC2 redundantly control neuronal development and are required for neuronal specification. Mice lacking HDAC1 or HDAC2 in neuronal precursors show no overt histoarchitectural phenotypes, whereas deletion of both HDAC1 and HDAC2 in developing neurons results in severe hippocampal abnormalities, absence of cerebellar foliation, disorganization of cortical neurons, and lethality by postnatal day 7. These abnormalities in brain formation can be attributed to a failure of neuronal precursors to differentiate into mature neurons and to excessive cell death. These results reveal redundant and essential roles for HDAC1 and HDAC2 in the progression of neuronal precursors to mature neurons in vivo.cerebellum ͉ hippocampus ͉ neurogenesis ͉ neuronal precursors H istone acetyltransferases (HATs) and histone deacetylases (HDACs) provide the enzymatic basis for transcriptional activation and repression, respectively, through alterations of the chromatin landscape (1). Transcription factors recruit HDACs, either individually, or in repressive complexes to deacetylate lysine residues on histone tails, resulting in chromatin condensation and repression of gene expression (2). There are 4 classes of HDACs that coordinate proper gene regulation for numerous cellular processes: class I (HDAC1, -2, -3, and -8), class II (HDAC4, -5, -6, -7, -9, and -10), sirtuin class III, and class IV (HDAC11) (3). Although much has been learned through in vitro and inhibitor studies, little is known about the biological function of these individual enzymes in vivo (4). We have shown that the class I HDACs, HDAC1 and HDAC2, redundantly regulate cardiac growth and morphogenesis (5), however, the functions of HDAC1 and HDAC2 in other tissues remain unknown.HDAC inhibitors have shown significant potential for therapeutic use in a variety of disorders, including those of the central nervous system (CNS), such as neurodegenerative disease, motor neuron disease, and a number of other neurological disease states (6). Furthermore, it has been shown that HDAC inhibitors induce differentiation of both embryonic and adult cortical neuronal progenitor cells to neurons specifically (7-9). The wide expression pattern of a number of HDACs in the developing brain suggests specific roles for individual HDACs in neuronal development (10), however, the broad inhibition of classical HDAC inhibitors has precluded the analysis of individual HDACs pharmacologically. Additionally, the early lethality associated with global deletion of class I HDACs in knockout mice has compounded the difficulties in analyzing the functions of these enzymes during specific stages of neurogenesis in vivo (5, 11).To further investigate the specific roles of HDAC1 and HDAC2 in neuronal development, we generated conditional deletions of HDAC1 and HDAC2 in the central nervous system. Here, we show both HDAC1 and HDAC2 are required for multip...

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“…The hda-1 mutation produced a highly penetrant, uncoordinated locomotion phenotype with severe defects in axon pathfinding, fasciculation of the nerve cord and neuronal cell migration (Zinovyeva et al, 2006).…”

Section: Hdac1 and Hdac2 In Heart Developmentmentioning

confidence: 99%

Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation

Brunmeir¹,

Lagger²,

Seiser³

2009

Int. J. Dev. Biol.

154

147

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During development from the fertilized egg to a multicellular organism, cell fate decisions have to be taken and cell lineage or tissue-specific gene expression patterns are created and maintained. These alterations in gene expression occur in the context of chromatin structure and are controlled by chromatin modifying enzymes. Gene disruption studies in different genetic systems have shown an essential role of various histone deacetylases (HDACs) during early development and cellular differentiation. In this review, we focus on the functions of the class I enzymes HDAC1 and HDAC2 during development in different organisms and summarise the current knowledge about their involvement in neurogenesis, myogenesis, haematopoiesis and epithelial cell differentiation. KEY WORDS: HDAC1, HDAC2, chromatin, differentiation, development Histone deacetylasesPosttranslational modifications of histones cause changes in the accessibility of DNA, thereby regulating many important cellular processes including transcription. Acetylation of core histones leads to a change in the net positive charge of histone tails and local opening of chromatin structure, a feature of transcriptionally active genes. On the other hand, deacetylated histone tails interact more closely with DNA and lead to a repressive state. Histone deacetylases (HDACs) catalyse the removal of acetyl groups from histone tails and are therefore considered as transcriptional corepressors. In addition to histones, HDACs also deacetylate non-histone proteins, such as the cytoskeletal protein tubulin (Hubbert et al., 2002) or transcription factors including p53 (Luo et al., 2000), E2F1 (MartinezBalbas et al., 2000) and YY1 (Yao et al., 2001). In fact, phylogenetic analysis suggests that the enzymatic activity was initially directed against non-histone proteins in a common ancestor devoid of histones (Gregoretti et al., 2004). In mammals, 18 deacetylases have been identified so far. These enzymes have been divided into 4 classes based on sequence similarity: Classic HDACs comprise class I (Saccharomyces cerevisiae Rpd3-like), class II (Saccharomyces cerevisiae Hda1-like) and class IV (HDAC11-like) enzymes. Class III consists of NAD-dependent, functionally unrelated Sir2-like deacetylases Int. J. Dev. Biol. 53: 275-289 (2009) Abbreviations used in this paper: HAT, histone acetyltransferase; HDA, HDAC, histone deacetylase; HDI, HDAC inhibitor; NuRD, nucleosome remodelling and deacetylase complex; Rpd3, reduced potassium dependency 3.named "sirtuins". Class I, II and IV HDACs are members of an ancient enzyme family, highly conserved throughout eukaryotic and prokaryotic evolution and are found in animals, plants, fungi, archaebacteria and eubacteria (Gregoretti et al., 2004). Class I histone deacetylasesPhylogenetic analysis revealed that class I genes in animals can be grouped into HDAC1/HDAC2, HDAC3 and HDAC8-like genes. Members of each subclass have been identified in protostomia (Oger et al., 2008) and deuterostomia. Species analysed so far carry orthologs (...

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The C. elegans histone deacetylase HDA-1 is required for cell migration and axon pathfinding

Cited by 17 publications

References 48 publications

Caenorhabditis elegansHistone Deacetylasehda-1Is Required for Morphogenesis of the Vulva and LIN-12/Notch-Mediated Specification of Uterine Cell Fates

Caenorhabditis elegansHistone Deacetylasehda-1Is Required for Morphogenesis of the Vulva and LIN-12/Notch-Mediated Specification of Uterine Cell Fates

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation

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