Cell & Development Biology and Genetics News

Mapping mouse hemangioblast maturation from headfold stages

2012-04-05T12:00:00Z

Perspective published in Developmental Biology

BIGGERBRAINS on Networking in your Research Career

2012-03-27T12:00:00Z

Interview with Prof Aldo Boccaccini. Department of Materials Science and Engineering University of Erlangen-Nuremberg, Germany, and Editor-in-Chief of Materials Letters. Interview focuses on the importance of networking in the early stages of your career.

Regulation of basal body and ciliary functions by Diversin [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development, Volume 128, Issues 7–10
Takayuki Yasunaga, Keiji Itoh, Sergei Y. Sokol
The centrosome is essential for the formation of the cilia and has been implicated in cell polarization and signaling during early embryonic development. A number of Wnt pathway components were found to localize at the centrosome, but how this localization relates to their signaling functions is unclear. In this study, we assessed a role for Diversin, a putative Wnt pathway mediator, in developmental processes that involve cilia. We find that Diversin is specifically localized to the basal body compartment near the base of the cilium in Xenopus multi-ciliated skin cells. Overexpression of Diversin RNA disrupted basal body polarization in these cells, suggesting that tightly regulated control of Diversin levels is crucial for this process. In cells depleted of endogenous Diversin, basal body structure appeared abnormal and this was accompanied by disrupted polarity, shortened or absent cilia and defective ciliary flow. These results are consistent with the involvement of Diversin in processes that are related to the acquisition of cell polarity and require ciliary functions.

Disruption of β-arrestins blocks glucocorticoid receptor and severely retards lung and liver development in mice [Mechanism of Developmentβ-arrestins blocks glucocorticoid receptor and severely retards lung and liver development in mice]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development, Volume 128, Issues 7–10
Mingfeng Zhang, Hongqi Teng, Jueping Shi, Yanding Zhang
In this study, the role of β-arrestin 1 and β-arrestin 2 in fetal lung and liver development was examined using Arrb1 ^−/− Arrb2 ^−/− mouse embryos. β-Arrestin 1/2 dual-null mice died shortly after birth and morphological examination revealed an obvious pulmonary hypoplasia and severe hepatic impairment. Western blot analysis demonstrated that GR protein levels in Arrb1 ^−/− Arrb2 ^−/− lung and liver tissues were significantly decreased compared to wild type embryos. Expression of GR proteins was confirmed in the nuclei of type II pneumocytes of 18.5 day embryos (E18.5) by immunofluorescence. The production of hepatic glucose and mRNA level of gluconeogenic enzymes were dramatically reduced in E18.5 Arrb1 ^−/− Arrb2 ^−/− liver. These results suggest that GR is an important downstream effector of the β-arrestin signaling pathway involved in regulation of lung and liver development. However, no obvious changes in GR expression following in vitro modulation of β-arrestin 1/2 indicated the existence of an indirect regulatory relationship between GR and the β-arrestin signaling pathway.

Angiotensin II stimulates in vitro branching morphogenesis of the isolated ureteric bud [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development, Volume 128, Issues 7–10
Renfang Song, Graeme Preston, Ihor V. Yosypiv
Mutations in the renin–angiotensin system (RAS) genes are associated with congenital anomalies of the kidney and urinary tract (CAKUT). As angiotensin (Ang) II, the principal effector peptide growth factor of the RAS, stimulates ureteric bud (UB) branching in whole intact embryonic (E) metanephroi, defects in UB morphogenesis may be causally linked to CAKUT observed under conditions of disrupted RAS. In the present study, using the isolated intact UB (iUB) assay, we tested the hypothesis that Ang II stimulates UB morphogenesis by directly acting on the UB, identified Ang II target genes in the iUB by microarray and examined the effect of Ang II on UB cell migration in vitro . We show that isolated E11.5 mouse iUBs express Ang II AT 1 and AT 2 receptor mRNA. Treatment of E11.5 iUBs grown in collagen matrix gels with Ang II (10⁻⁵ M) increases the number of iUB tips after 48 h of culture compared to control (4.8 ± 0.4 vs. 2.4 ± 0.2, p < 0.01). A number of genes required for UB branching as well as novel genes whose role in UB development is currently unknown are targets of Ang II signaling in the iUB. In addition, Ang II increases UB cell migration (346 ± 5.1 vs. 275 ± 4.4, p < 0.01) in vitro . In summary, Ang II stimulates UB cell migration and directly induces morphogenetic response in the iUB. We conclude that Ang II-regulated genes in the iUB may be important mediators of Ang II-induced UB branching. We hypothesize that Ang II-dependent cell movements play an important role in UB branching morphogenesis.

The role of canonical Wnt signaling in leg regeneration and metamorphosis in the red flour beetle Tribolium castaneum [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development, Volume 128, Issues 7–10
Mita V. Shah, Erica K.O. Namigai, Yuichiro Suzuki
Many organisms across the Metazoa have regenerative abilities with potentially conserved genetic mechanisms that can enlighten both medicine and evolutionary studies. Here, the role of canonical Wnt signaling was examined in the red flour beetle Tribolium castaneum in order to explore its role during metamorphosis and larval leg regeneration. Double-stranded RNA mediated silencing of Wnt-1 signaling resulted in a loss of wings and appendages with a dramatic reduction in width, indicating that the Wnt-1 signaling pathway is necessary for proper post-embryonic appendage development in T. castaneum. Furthermore, disruption of canonical Wnt signaling led to the complete impairment of limb regeneration in T. castaneum . Our findings suggest that Wnt-1 signaling is a conserved mechanism for appendage development across all holometabolous insects and indicate that the role of Wnt-1 signaling in limb regeneration has been retained across all insects as various modes of limb development evolved. Importantly, this study shows that the availability of the genome sequence and the ease of performing leg ablations make Tribolium an excellent holometabolous insect model for studying regeneration.

Fgf is required to regulate anterior–posterior patterning in the Xenopus lateral plate mesoderm [Mechanism of Development–posterior patterning in the Xenopus lateral plate mesoderm]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development, Volume 128, Issues 7–10
Steven J. Deimling, Thomas A. Drysdale
Given that the lateral plate mesoderm (LPM) gives rise to the cardiovascular system, identifying the cascade of signalling events that subdivides the LPM into distinct regions during development is an important question. Retinoic acid (RA) is known to be necessary for establishing the expression boundaries of important transcription factors that demarcate distinct regions along the anterior posterior axis of the LPM. Here, we demonstrate that fibroblast growth factor (Fgf) signalling is also necessary for regulating the expression domains of the same transcription factors ( nkx2.5 , foxf1 , hand1 and sall3 ) by restricting the RA responsive LPM domains. When Fgf signalling is inhibited in neurula stage embryos, the more posterior LPM expression domains are lost, while the more anterior domains are extended further posterior. The domain changes are maintained throughout development as Fgf inhibition results in similar domain changes in late stage embryos. We also demonstrate that Fgf signalling is necessary for both the initiation of heart specification, and for maintaining heart specification until overt differentiation occurs. Fgf signalling is also necessary to restrict vascular patterning and create a vascular free domain in the posterior end of the LPM that correlates with the expression of hand1 . Finally, we show cross talk between the RA and Fgf signalling pathways in the patterning of the LPM. We suggest that this tissue wide patterning event, active during the neurula stage, is an initial step in regional specification of the LPM, and this process is an essential early event in LPM patterning.

Control of Cdc14 activity coordinates cell cycle and development in Caenorhabditis elegans [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development, Volume 128, Issues 7–10
Sarah H. Roy, Joseph E. Clayton, Jenna Holmen, Eleanor Beltz, R. Mako Saito
Much of our understanding of the function and regulation of the Cdc14 family of dual-specificity phosphatases originates from studies in yeasts. In these unicellular organisms Cdc14 is an important regulator of M-phase events. In contrast, the Caenorhabditis elegans homolog, cdc-14 , is not necessary for mitosis, rather it is crucial for G 1 /S regulation to establish developmental cell-cycle quiescence. Despite the importance of integrating cdc-14 regulation with development, the mechanisms by which this coordination occurs are largely unknown. Here, we demonstrate that several processes conspire to focus the activity of cdc-14 . First, the cdc-14 locus can produce at least six protein variants through alternative splicing. We find that a single form, CDC-14C, is the key variant acting during vulva development. Second, CDC-14C expression is limited to a subset of cells, including vulva precursors, through post-transcriptional regulation. Lastly, the CDC-14C subcellular location, and thus its potential interactions with other regulatory proteins, is regulated by nucleocytoplasmic shuttling. We find that the active export of CDC-14C from the nucleus during interphase is dependent on members of the Cyclin D and Crm1 families. We propose that these mechanisms collaborate to restrict the activity of cdc-14 as central components of an evolutionarily conserved regulatory network to coordinate cell-cycle progression with development.

Contents [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development, Volume 128, Issues 7–10

Retraction notice to ‘Drosophila Ten-a is a maternal pair-rule and patterning gene’ [Mech. Dev. 124 (2007) 911–924] [Mechanism of Development‘Drosophila Ten-a is a maternal pair-rule and patterning gene’ [Mech. Dev. 124 (2007) 911–924]]

2012-03-27T12:00:00Z

Publication year: 2011
Source:Mechanisms of Development
Nadya Rakovitsky, Yosef Buganim, Tomer Swissa, Yael Kinel-Tahan, Shirly Brenner, Malkiel A. Cohen, Anna Levine, Ron Wides

A lineage specific enhancer drives Otx2 expression in teleost organizer tissues [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Daisuke Kurokawa, Tomomi Ohmura, Koji Akasaka, Shinichi Aizawa
In mouse Otx2 plays essential roles in anterior–posterior axis formation and head development in anterior visceral endoderm and anterior mesendoderm. The Otx2 expression in these sites is regulated by VE and CM enhancers at the 5′ proximal to the translation start site, and we proposed that these enhancers would have been established in ancestral sarcoptergians after divergence from actinopterigians for the use of Otx2 as the head organizer gene ( Kurokawa et al., 2010 ). This would make doubtful an earlier proposal of ours that a 1.1 kb fragment located at +14.4 to +15.5 kb 3′ (3′En) of fugu Otx2a gene harbors enhancers phylogenetically and functionally homologous to mouse VE and CM enhancers ( Kimura-Yoshida et al., 2007 ). In the present study, we demonstrate that fugu Otx2a is not expressed in the dorsal margin of blastoderm, shield and early anterior mesendoderm, and that the fugu Otx2a 3′En do not exhibit activities at these sites of fugu embryos. We conclude that the fugu Otx2a 3′En does not harbor an organizer enhancer, but encodes an enhancer for the expression in later anterior mesendodermal tissues. Instead, in fugu embryos Otx2b is expressed in the dorsal margin of blastoderm at blastula stage and shield at 50% epiboly, and this expression is directed by an enhancer, 5′En, located at −1000 to −800 bp, which is uniquely conserved among teleost Otx2b orthologues.

p21, an important mediator of quiescence during pituitary tumor formation, is dispensable for normal pituitary development during embryogenesis [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Pamela Monahan, Ashley D. Himes, Agata Parfieniuk, Lori T. Raetzman
A delicate balance between proliferation and differentiation must be maintained in the developing pituitary to ensure the formation of the appropriate number of hormone producing cells. In the adult, proliferation is actively restrained to prevent tumor formation. The cyclin dependent kinase inhibitors (CDKIs) of the CIP/KIP family, p21, p27 and p57, mediate cell cycle inhibition. Although p21 is induced in the pituitary upon loss of Notch signaling or initiation of tumor formation to halt cell cycle progression, its role in normal pituitary organogenesis has not been explored. In wildtype pituitaries, expression of p21 is limited to a subset of cells embryonically as well as during the postnatal proliferative phase. Mice lacking p21 do not have altered cell proliferation during early embryogenesis, but do show a slight delay in separation of proliferating progenitors from the oral ectoderm. By embryonic day 16.5, p21 mutants have an alteration in the spatial distribution of proliferating pituitary progenitors, however there is no overall change in proliferation. At postnatal day 21, there appears to be no change in proliferation, as assessed by cells expressing Ki67 protein. However, p21 mutant pituitaries have significantly less mRNA of Myc and the cyclins Ccnb1 , Ccnd1 , Ccnd2 and Ccne1 than wildtype pituitaries. Interestingly, unlike the redundant role in cell cycle inhibition uncovered in p27 / p57 double mutants, the pituitary of p21 / p27 double mutants has a similar proliferation profile to p27 single mutants at the time points examined. Taken together, these studies demonstrate that unlike p27 or p57, p21 does not play a major role in control of progenitor proliferation in the developing pituitary. However, p21 may be required to maintain normal levels of cell cycle components.

Canonical Wnt signaling in the visceral muscle is required for left–right asymmetric development of the Drosophila midgut [Mechanism of Development–right asymmetric development of the Drosophila midgut]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Junpei Kuroda, Mitsutoshi Nakamura, Masashi Yoshida, Haruka Yamamoto, Takaaki Maeda, Kiichiro Taniguchi, Naotaka Nakazawa, Ryo Hatori, Akira Ishio, Ayumi Ozaki, Shunsuke Shimaoka, Tamiko Ito, Hironao Iida, Takashi Okumura, Reo Maeda, Kenji Matsuno
Many animals develop left–right (LR) asymmetry in their internal organs. The mechanisms of LR asymmetric development are evolutionarily divergent, and are poorly understood in invertebrates. Therefore, we studied the genetic pathway of LR asymmetric development in Drosophila . Drosophila has several organs that show directional and stereotypic LR asymmetry, including the embryonic gut, which is the first organ to develop LR asymmetry during Drosophila development. In this study, we found that genes encoding components of the Wnt-signaling pathway are required for LR asymmetric development of the anterior part of the embryonic midgut (AMG). frizzled 2 ( fz2 ) and Wnt4 , which encode a receptor and ligand of Wnt signaling, respectively, were required for the LR asymmetric development of the AMG. arrow ( arr ), an ortholog of the mammalian gene encoding low-density lipoprotein receptor-related protein 5/6, which is a co-receptor of the Wnt-signaling pathway, was also essential for LR asymmetric development of the AMG. These results are the first demonstration that Wnt signaling contributes to LR asymmetric development in invertebrates, as it does in vertebrates. The AMG consists of visceral muscle and an epithelial tube. Our genetic analyses revealed that Wnt signaling in the visceral muscle but not the epithelium of the midgut is required for the AMG to develop its normal laterality. Furthermore, fz2 and Wnt4 were expressed in the visceral muscles of the midgut. Consistent with these results, we observed that the LR asymmetric rearrangement of the visceral muscle cells, the first visible asymmetry of the developing AMG, did not occur in embryos lacking Wnt4 expression. Our results also suggest that canonical Wnt/β-catenin signaling, but not non-canonical Wnt signaling, is responsible for the LR asymmetric development of the AMG. Canonical Wnt/β-catenin signaling is reported to have important roles in LR asymmetric development in zebrafish. Thus, the contribution of canonical Wnt/β-catenin signaling to LR asymmetric development may be an evolutionarily conserved feature between vertebrates and invertebrates.

Retinoic acid metabolism links the periodical differentiation of germ cells with the cycle of Sertoli cells in mouse seminiferous epithelium [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Ryo Sugimoto, Yo-ichi Nabeshima, Shosei Yoshida
Homeostasis of tissues relies on the regulated differentiation of stem cells. In the epithelium of mouse seminiferous tubules, the differentiation process from undifferentiated spermatogonia (A undiff ), which harbor the stem cell functions, to sperm occurs in a periodical manner, known as the “seminiferous epithelial cycle”. To identify the mechanism underlying this periodic differentiation, we investigated the roles of Sertoli cells (the somatic supporting cells) and retinoic acid (RA) in the seminiferous epithelial cycle. Sertoli cells cyclically change their functions in a coordinated manner with germ cell differentiation and support the entire process of spermatogenesis. RA is known to play essential roles in this periodic differentiation, but its precise mode of action and its regulation remains largely obscure. We showed that an experimental increase in RA signaling was capable of both inducing A undiff differentiation and resetting the Sertoli cell cycle to the appropriate stage. However, these actions of exogenous RA signaling on A undiff and Sertoli cells were strongly interfered by the differentiating germ cells of intimate location. Based on the expression of RA metabolism-related genes among multiple cell types – including germ and Sertoli cells – and their regulation by RA signaling, we propose here that differentiating germ cells play a primary role in modulating the local RA metabolism, which results in the timed differentiation of A undiff and the appropriate cycling of Sertoli cells. Similar regulation by differentiating progeny through the modulation of local environment could also be involved in other stem cell systems.

Fate maps of ventral and dorsal pancreatic progenitor cells in early somite stage mouse embryos [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Rika Miki, Tetsu Yoshida, Kazuya Murata, Shinya Oki, Kazuhiko Kume, Shoen Kume
The origins of liver progenitor cells have been extensively studied, but evidence on the origin of pancreatic precursor cells is currently limited. Pancreatic and duodenal homeobox gene 1 ( Pdx1 ) is one of the earliest known markers for the pancreas. A transgenic mouse line expressing green fluorescent protein (GFP) under the control of the Pdx1 promoter showed that Pdx1 /GFP expression was first observed in the mid-region of the anterior intestinal portal (AIP) lip at embryonic day (E) 8.5 at the 5–6 somite stage (ss). The liver progenitors were confirmed to originate from separate domains at the lateral endoderm and the inner part of the medial AIP as previously reported ( Tremblay and Zaret, 2005 ), which turned out to lie caudally to the Pdx1 /GFP-expressing domain. To confirm if the early Pdx1 /GFP-positive cells give rise to the pancreatic bud, we labeled the cells on the lip of the AIP using the carbocyanine dye CM-DiI and traced their fates in 1–4 ss, 5–6 ss and 7–9 ss E8.5 embryos using an ex utero whole embryo culture method. At 1 ss, the ventral pancreas progenitors were observed in the lateral endoderm, not yet being segregated from the liver or gut progenitors. Cells that contributed solely to the ventral pancreas first appeared at the AIP lip from 5 ss. At 5–6 ss, cells from the medial of the AIP lip contributed to the ventral pancreas. The pancreas fate region become narrower as development progresses. At 7–9 ss, the cells contributing to the ventral pancreas resided in a narrow region of the AIP lip. From 5 ss, the right flanking region contributes to the posterior gut, and the left flanking region contributes to the anterior gut. Dorsal pancreatic progenitors originate from the dorsal endoderm at the 3–6 somite level at 7–9 ss, though they have not yet diverged from the dorsal gut progenitors at this stage.

Mouse germ cell clusters form by aggregation as well as clonal divisions [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Lindsey Mork, Hao Tang, Iordan Batchvarov, Blanche Capel
After their arrival in the fetal gonad, mammalian germ cells express E-cadherin and are found in large clusters, similar to germ cell cysts in Drosophila . In Drosophila , germ cells in cysts are connected by ring canals. Several molecular components of intercellular bridges in mammalian cells have been identified, including TEX14, a protein required for the stabilization of intercellular bridges, and several associated proteins that are components of the cytokinesis complex. This has led to the hypothesis that germ cell clusters in the mammalian gonad arise through incomplete cell divisions. We tested this hypothesis by generating chimeras between GFP-positive and GFP-negative mice. We show that germ cell clusters in the fetal gonad arise through aggregation as well as cell division. Intercellular bridges, however, are likely restricted to cells of the same genotype.

Neucrin, a novel secreted antagonist of canonical Wnt signaling, plays roles in developing neural tissues in zebrafish [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Ayumi Miyake, Satoka Nihno, Yuino Murakoshi, Ayano Satsuka, Yoshiaki Nakayama, Nobuyuki Itoh
Wnt signaling plays crucial roles in neural development. We previously identified Neucrin, a neural-specific secreted antagonist of canonical Wnt/β-catenin signaling, in humans and mice. Neucrin has one cysteine-rich domain, in which the positions of 10 cysteine residues are similar to those in the second cysteine-rich domain of Dickkopfs, secreted Wnt antagonists. Here, we have identified zebrafish neucrin to understand its roles in vivo . Zebrafish Neucrin also has one cysteine-rich domain, which is significantly similar to that of mouse Neucrin. Zebrafish neucrin was also predominantly expressed in developing neural tissues. To examine roles of neucrin in neural development, we analyzed neucrin knockdown embryos. Neural development in zebrafish embryos was impaired by the knockdown of neucrin . The knockdown of neucrin caused increased expression of the Wnt/β-catenin target genes. In contrast, overexpression of neucrin reduced the expression of the Wnt/β-catenin target genes. The knockdown of neucrin affected specification of dorsal region in the midbrain and hindbrain. The knockdown of neucrin also suppressed neuronal differentiation and caused increased cell proliferation and apoptosis in developing neural tissues. Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues and plays roles in neural development in zebrafish.

Regulation of PP2A activity by Mid1 controls cranial neural crest speed and gangliogenesis [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Elizabeth J. Latta, Jon P. Golding
X-linked Opitz syndrome (XLOS), caused by mutation in the MID1 gene, is a midline malformation syndrome with obvious craniofacial abnormalities. Because cranial neural crest cells (CNC) play a pivotal role in cranial morphogenesis, we examined the spatio-temporal expression of cMid1 in chick embryos and investigated if alterations in Mid1 protein function, specifically the ability of Mid1 to negatively regulate levels of protein phosphatase 2A (PP2A), affected CNC survival or migration. During the main phase of CNC migration (stage 9 to 11) cMid1 is strongly expressed within r2 and a subset of CNC in cranial mesenchyme at the level of r1/2 to the isthmus, but is not expressed in more caudal CNC streams. Inhibiting cMid1 function in r2 elevated PP2A levels. Overexpression of PP2A in r2 slowed CNC migration in vitro and in ovo and inhibited trigeminal gangliogenesis. Conversely in r4, forced expression of cMid1 , or pharmacological inhibition of PP2A lowered PP2A levels. Inhibition of PP2A in r4 CNC in vitro up-regulated the disintegrin and metalloprotease ADAM10 and selectively increased CNC motility on fibronectin and collagen substrates, but not on laminin. In ovo , inhibiting PP2A activity in r4 increased CNC migration and hastened formation of the geniculate/vestibuloacoustic ganglion, comprising mostly epibranchial placode neuroblasts. Placodal neuroblast migration into the cranial mesenchyme is known to depend on the presence of r4 CNC and we show that inhibition of PP2A in r4 CNC causes premature breakdown of the epibranchial placode basement membrane and early immigration of placodal neuroblasts. In all cases, CNC proliferation and death were unaffected by altered PP2A levels. We propose that factors capable of altering PP2A activity, such as Mid1, affect CNC motility and matrix remodeling, thereby modulating craniofacial development.

CCDC-55 is required for larval development and distal tip cell migration in Caenorhabditis elegans [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Ismar Kovacevic, Richard Ho, Erin J. Cram
The Caenorhabditis elegans distal tip cells (DTCs) are an in vivo model for the study of developmentally regulated cell migration. In this study, we characterize a novel role for CCDC-55, a conserved coiled-coil domain containing protein, in DTC migration and larval development in C. elegans . Although animals homozygous for a probable null allele, ccdc - 55 ( ok2851 ), display an early larval arrest, RNAi depletion experiments allow the analysis of later phenotypes and suggest that CCDC-55 is needed within the DTC for migration to cease at the end of larval morphogenesis. The ccdc - 55 gene is found in an operon with rnf - 121 and rnf - 5 , E3 ubiquitin ligases that target cell migration genes such as the β-integrin PAT-3. Genetic interaction studies using RNAi depletion and the deletion alleles rnf - 121 ( ok848 ) and rnf - 5 ( tm794 ) indicate that CCDC-55 and the RNF genes act at least partially in parallel to promote termination of cell migration in the adult DTC.

Regulation of Polycomb group genes Psc and Su(z)2 in Drosophila melanogaster [Mechanism of Development]

2012-03-27T12:00:00Z

Publication year: 2012
Source:Mechanisms of Development, Volume 128, Issues 11–12
Sung Yeon Park, Yuri B. Schwartz, Tatyana G. Kahn, Dalal Asker, Vincenzo Pirrotta
Certain Polycomb group (PcG) genes are themselves targets of PcG complexes. Two of these constitute the Drosophila Psc – Su(z)2 locus, a region whose chromatin is enriched for H3K27me3 and contains several putative Polycomb response elements (PREs) that bind PcG proteins. To understand how PcG mechanisms regulate this region, the repressive function of the PcG protein binding sites was analyzed using reporter gene constructs. We find that at least two of these are functional PREs that can silence a reporter gene in a PcG-dependent manner. One of these two can also display anti-silencing activity, dependent on the context. A PcG protein binding site near the Psc promoter behaves not as a silencer but as a down-regulation module that is actually stimulated by the Pc gene product but not by other PcG products. Deletion of one of the PREs increases the expression level of Psc and Su(z)2 by twofold at late embryonic stages. We present evidence suggesting that the Psc – Su(z)2 locus is flanked by insulator elements that may protect neighboring genes from inappropriate silencing. Deletion of one of these regions results in extension of the domain of H3K27me3 into a region containing other genes, whose expression becomes silenced in the early embryo.