hox Gene Regulation and Function During Zebrafish Embryogenesis: A Dissertation

Hox genes encode a conserved family of homeodomain containing transcription factors essential for metazoan development. The establishment of overlapping Hox expression domains specifies tissue identities along the anterior-posterior axis during early embryogenesis and is regulated by chromatin architecture and retinoic acid (RA). Here we present the role nucleosome positioning plays in hox activation during embryogenesis. Using four stages of early embryo development, we map nucleosome positions at 37 zebrafish hox promoters. We find nucleosome arrangement to be progressive, taking place over several stages independent of RA. This progressive change in nucleosome arrangement on invariant sequence suggests that trans-factors play an important role in organizing nucleosomes. To further test the role of trans-factors, we created hoxb1b and hoxb1a mutants to determine if the loss of either protein effected nucleosome positions at the promoter of a known target, hoxb1a. Characterization of these mutations identified hindbrain segmentation defects similar to targeted deletions of mouse orthologs Hoxa1 and Hoxb1 and zebrafish hoxb1b and hoxb1a morpholino (MO) loss-of-function experiments. However, we also identified differences in hindbrain segmentation as well as phenotypes in facial motor neuron migration and reticulospinal neuron formation not previously observed in the MO experiments. Finally, we find that nucleosomes at the hoxb1a promoter are positioned differently in hoxb1b-/- embryos compared to wild-type. Together, our data provides new insight into the roles of hoxb1b and hoxb1a in zebrafish hindbrain segmentation and reticulospinal neuron formation and indicates that nucleosome positioning at hox promoters is dynamic, depending on sequence specific factors such as Hox proteins

Quand l’uniforme fait l’homme libre

Cet article analyse le rôle des vêtements dans la métamorphose d’esclaves afro-américains en soldats de l’Union pendant la Guerre civile (1861-1865). Il explore la manière et la raison pour laquelle les uniformes militaires portent un tel poids narratif dans les portraits de ces hommes. Les textes, images, objets, gravures et photographies sont étudiés dans le contexte de la perception du corps au xixe siècle et des nouvelles théories de l’anthropologie physique et de la phrénologie. L’article souligne le rôle de ces images dans la construction d’un discours cohérent sur la rédemption de l’esclavage et d’une catégorie « homme » plus inclusive, plus universelle, fondée sur le service militaire.This article examines clothing’s role in the transformation of African American slaves into Union soldiers during the American Civil War (1861-1865), exploring how and why military uniforms bore narrative weight in visual depictions of these men. Text, images, material objects, prints and photographs are examined within the context of nineteenth-century American conceptions of bodily management, posture, and developing theories on physical anthropology and phrenology. The article highlights the role of these images in constructing both a coherent narrative of redemption from slavery and a more inclusive, universal category of “men” that was linked to military service

To look like men of war: visual transformation narratives of African American Union Soldiers

This article examines clothing’s role in the transformation of African American slaves into Union soldiers during the American Civil War (1861-1865), exploring how and why military uniforms bore narrative weight in visual depictions of these men. Text, images, material objects, prints and photographs are examined within the context of nineteenth-century American conceptions of bodily management, posture, and developing theories on physical anthropology and phrenology. The article highlights the role of these images in constructing both a coherent narrative of redemption from slavery and a more inclusive, universal category of “men” that was linked to military service.Cet article analyse le rôle des vêtements dans la métamorphose d’esclaves afro-américains en soldats de l’Union pendant la Guerre civile (1861-1865). Il explore la manière et la raison pour laquelle les uniformes militaires portent un tel poids narratif dans les portraits de ces hommes. Les textes, images, objets, gravures et photographies sont étudiés dans le contexte de la perception du corps au xixe siècle et des nouvelles théories de l’anthropologie physique et de la phrénologie. L’article souligne le rôle de ces images dans la construction d’un discours cohérent sur la rédemption de l’esclavage et d’une catégorie « homme » plus inclusive, plus universelle, fondée sur le service militaire

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Targeted germ line disruptions reveal general and species-specific roles for paralog group 1 hox genes in zebrafish

BACKGROUND: The developing vertebrate hindbrain is transiently segmented into rhombomeres by a process requiring Hox activity. Hox genes control specification of rhombomere fates, as well as the stereotypic differentiation of rhombomere-specific neuronal populations. Accordingly, germ line disruption of the paralog group 1 (PG1) Hox genes Hoxa1 and Hoxb1 causes defects in hindbrain segmentation and neuron formation in mice. However, antisense-mediated interference with zebrafish hoxb1a and hoxb1b (analogous to murine Hoxb1 and Hoxa1, respectively) produces phenotypes that are qualitatively and quantitatively distinct from those observed in the mouse. This suggests that PG1 Hox genes may have species-specific functions, or that anti-sense mediated interference may not completely inactivate Hox function in zebrafish. RESULTS: Using zinc finger and TALEN technologies, we disrupted hoxb1a and hoxb1b in the zebrafish germ line to establish mutant lines for each gene. We find that zebrafish hoxb1a germ line mutants have a more severe phenotype than reported for Hoxb1a antisense treatment. This phenotype is similar to that observed in Hoxb1 knock out mice, suggesting that Hoxb1/hoxb1a have the same function in both species. Zebrafish hoxb1b germ line mutants also have a more severe phenotype than reported for hoxb1b antisense treatment (e.g. in the effect on Mauthner neuron differentiation), but this phenotype differs from that observed in Hoxa1 knock out mice (e.g. in the specification of rhombomere 5 (r5) and r6), suggesting that Hoxa1/hoxb1b have species-specific activities. We also demonstrate that Hoxb1b regulates nucleosome organization at the hoxb1a promoter and that retinoic acid acts independently of hoxb1b to activate hoxb1a expression. CONCLUSIONS: We generated several novel germ line mutants for zebrafish hoxb1a and hoxb1b. Our analyses indicate that Hoxb1 and hoxb1a have comparable functions in zebrafish and mouse, suggesting a conserved function for these genes. In contrast, while Hoxa1 and hoxb1b share functions in the formation of r3 and r4, they differ with regards to r5 and r6, where Hoxa1 appears to control formation of r5, but not r6, in the mouse, whereas hoxb1b regulates formation of r6, but not r5, in zebrafish. Lastly, our data reveal independent regulation of hoxb1a expression by retinoic acid and Hoxb1b in zebrafish

Cell identity switching regulated by retinoic acid signaling maintains homogeneous segments in the hindbrain

© 2018 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.devcel.2018.04.003The patterning of tissues to form subdivisions with distinct and homogeneous regional identity is potentially disrupted by cell intermingling. Transplantation studies suggest that homogeneous segmental identity in the hindbrain is maintained by identity switching of cells that intermingle into another segment. We show that switching occurs during normal development and is mediated by feedback between segment identity and the retinoic acid degrading enzymes, cyp26b1 and cyp26c1. egr2, which specifies the segmental identity of rhombomeres r3 and r5, underlies the lower expression level of cyp26b1 and cyp26c1 in r3 and r5 compared with r2, r4, and r6. Consequently, r3 or r5 cells that intermingle into adjacent segments encounter cells with higher cyp26b1/c1 expression, which we find is required for downregulation of egr2b expression. Furthermore, egr2b expression is regulated in r2, r4, and r6 by non-autonomous mechanisms that depend upon the number of neighbors that express egr2b. These findings reveal that a community regulation of retinoid signaling maintains homogeneous segmental identity.This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK ( FC001217 ), the UK Medical Research Council ( FC001217 ), and the Wellcome Trust ( FC001217).Published versio

Angeborener Schwachsinn bei Zwillingen

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