Recent CIG publications Archive

Elife. 2021 Mar 5;10:e63036. doi: 10.7554/eLife.63036. Online ahead of print.

Targeted molecular profiling of rare olfactory sensory neurons identifies fate, wiring and functional determinants

J Roman Arguello ¹, Liliane Abuin ¹, Jan Armida ¹, Kaan Mika ¹, Phing Chian Chai ¹, Richard Benton ¹Affiliations expand

Free article

Abstract

Determining the molecular properties of neurons is essential to understand their development, function and evolution. Using Targeted DamID (TaDa), we characterize RNA polymerase II occupancy and chromatin accessibility in selected Ionotropic receptor (Ir)-expressing olfactory sensory neurons in Drosophila. Although individual populations represent a minute fraction of cells, TaDa is sufficiently sensitive and specific to identify the expected receptor genes. Unique Ir expression is not consistently associated with differences in chromatin accessibility, but rather to distinct transcription factor profiles. Genes that are heterogeneously-expressed across populations are enriched for neurodevelopmental factors, and we identify functions for the POU-domain protein Pdm3 as a genetic switch of Ir neuron fate, and the atypical cadherin Flamingo in segregation of neurons into discrete glomeruli. Together this study reveals the effectiveness of TaDa in profiling rare neural populations, identifies new roles for a transcription factor and a neuronal guidance molecule, and provides valuable datasets for future exploration.

Keywords: D. melanogaster; developmental biology; neuroscience.

• PMID: 33666172
• DOI: 10.7554/eLife.63036

Methods Mol Biol. 2021;2297:21-31. doi: 10.1007/978-1-0716-1370-2_3.

Analysis of Shade-Induced Hypocotyl Elongation in Arabidopsis

Yetkin Çaka Ince ¹, Vinicius Costa Galvão ²Affiliations expand

Abstract

The presence of neighbor or overtopping plants is perceived by changes in light quality, which lead to several growth and developmental changes known as shade avoidance syndrome (SAS). Among them, the analysis of hypocotyl elongation is an important SAS physiological output that has been successfully used to investigate photoreceptors and downstream signaling components. Here we describe the experimental setup and growth conditions used to investigate photoreceptors and their signaling mechanisms through the analysis of hypocotyl elongation in laboratory, using simulated low R/FR ratio, low blue light, and true/deep shade conditions.

Keywords: Hypocotyl; Low R/FR ratio; Low blue; Shade avoidance; True shade.

• PMID: 33656666
• DOI: 10.1007/978-1-0716-1370-2_3

Nat Commun. 2021 Mar 1;12(1):1360. doi: 10.1038/s41467-021-21589-3.

Transcription organizes euchromatin via microphase separation

Lennart Hilbert ^{1 2 3 4 5}, Yuko Sato ^# 6, Ksenia Kuznetsova ^# 2, Tommaso Bianucci ^# 2 3, Hiroshi Kimura ⁶, Frank Jülicher ^1 3 7 8, Alf Honigmann ², Vasily Zaburdaev ^1 3 9, Nadine L Vastenhouw ^10 11

Free article

Abstract

In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for transcription, is spatially organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity. While transcription and RNA have been implicated in euchromatin organization, it remains unclear how their interplay forms and maintains transcription pockets. Here we combine theory and experiment to analyze the dynamics of euchromatin organization as pluripotent zebrafish cells exit mitosis and begin transcription. We show that accumulation of RNA induces formation of transcription pockets which displace transcriptionally inactive chromatin. We propose that the accumulating RNA recruits RNA-binding proteins that together tend to separate from transcriptionally inactive euchromatin. Full phase separation is prevented because RNA remains tethered to transcribed euchromatin through RNA polymerases. Instead, smaller scale microphases emerge that do not grow further and form the typical pattern of euchromatin organization.

• PMID: 33649325
• DOI: 10.1038/s41467-021-21589-3

Hum Brain Mapp. 2021 Feb 21. doi: 10.1002/hbm.25354. Online ahead of print.

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Ida E Sønderby ^1 2 3, Christopher R K Ching ⁴, Sophia I Thomopoulos ⁴, Dennis van der Meer ^2 5, Daqiang Sun ^6 7, Julio E Villalon-Reina ⁴, Ingrid Agartz ^8 9 10, Katrin Amunts ^11 12, Celso Arango ^13 14, Nicola J Armstrong ¹⁵, Rosa Ayesa-Arriola ^14 16, Geor Bakker ^17 18, Anne S Bassett ^19 20 21, Dorret I Boomsma ^22 23, Robin Bülow ²⁴, Nancy J Butcher ^21 25, Vince D Calhoun ²⁶, Svenja Caspers ^11 27, Eva W C Chow ^19 21, Sven Cichon ^11 28 29, Simone Ciufolini ³⁰, Michael C Craig ³¹, Benedicto Crespo-Facorro ³², Adam C Cunningham ³³, Anders M Dale ^34 35, Paola Dazzan ³⁶, Greig I de Zubicaray ³⁷, Srdjan Djurovic ^1 38, Joanne L Doherty ^33 39, Gary Donohoe ⁴⁰, Bogdan Draganski ^41 42, Courtney A Durdle ⁴³, Stefan Ehrlich ⁴⁴, Beverly S Emanuel ⁴⁵, Thomas Espeseth ^46 47, Simon E Fisher ^48 49, Tian Ge ^50 51, David C Glahn ^52 53, Hans J Grabe ^54 55, Raquel E Gur ^56 57, Boris A Gutman ⁵⁸, Jan Haavik ^59 60, Asta K Håberg ^61 62, Laura A Hansen ⁶³, Ryota Hashimoto ^64 65, Derrek P Hibar ⁶⁶, Avram J Holmes ^67 68, Jouke-Jan Hottenga ²², Hilleke E Hulshoff Pol ⁶⁹, Maria Jalbrzikowski ⁷⁰, Emma E M Knowles ^51 71, Leila Kushan ⁷², David E J Linden ^73 74, Jingyu Liu ^26 75, Astri J Lundervold ⁷⁶, Sandra Martin-Brevet ⁴¹, Kenia Martínez ^13 14 77, Karen A Mather ^78 79, Samuel R Mathias ^53 71, Donna M McDonald-McGinn ^45 80 81, Allan F McRae ⁸², Sarah E Medland ⁸³, Torgeir Moberget ⁸⁴, Claudia Modenato ^41 85, Jennifer Monereo Sánchez ^73 86 87, Clara A Moreau ⁸⁸, Thomas W Mühleisen ^11 12 29, Tomas Paus ^89 90, Zdenka Pausova ⁹¹, Carlos Prieto ⁹², Anjanibhargavi Ragothaman ⁹³, Céline S Reinbold ^29 94, Tiago Reis Marques ^30 95, Gabriela M Repetto ⁹⁶, Alexandre Reymond ⁹⁷, David R Roalf ⁵⁶, Borja Rodriguez-Herreros ⁹⁸, James J Rucker ³⁶, Perminder S Sachdev ^78 99, James E Schmitt ¹⁰⁰, Peter R Schofield ^79 101, Ana I Silva ^74 102, Hreinn Stefansson ¹⁰³, Dan J Stein ¹⁰⁴, Christian K Tamnes ^2 9 105, Diana Tordesillas-Gutiérrez ^14 106, Magnus O Ulfarsson ^103 107, Ariana Vajdi ⁷², Dennis van ‘t Ent ²², Marianne B M van den Bree ³³, Evangelos Vassos ¹⁰⁸, Javier Vázquez-Bourgon ^14 16 109, Fidel Vila-Rodriguez ¹¹⁰, G Bragi Walters ^103 111, Wei Wen ⁷⁸, Lars T Westlye ^3 46 112, Katharina Wittfeld ^54 55, Elaine H Zackai ^45 80, Kári Stefánsson ^103 111, Sebastien Jacquemont ^88 113, Paul M Thompson ⁴, Carrie E Bearden ^6 114, Ole A Andreassen ², ENIGMA-CNV Working Group; ENIGMA 22q11.2 Deletion Syndrome Working GroupAffiliations expand

Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype-first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

• PMID: 33615640
• DOI: 10.1002/hbm.25354

Genes Dev. 2021 Feb 18. doi: 10.1101/gad.346460.120. Online ahead of print.

Circadian hepatocyte clocks keep synchrony in the absence of a master pacemaker in the suprachiasmatic nucleus or other extrahepatic clocks

Flore Sinturel ^{# 1 2 3 4}, Pascal Gos ^# 5, Volodymyr Petrenko ^1 2 3 4, Claudia Hagedorn ⁶, Florian Kreppel ⁶, Kai-Florian Storch ⁷, Darko Knutti ⁷, Andre Liani ⁵, Charles Weitz ⁷, Yann Emmenegger ⁸, Paul Franken ⁸, Luigi Bonacina ⁹, Charna Dibner ^1 2 3 4, Ueli Schibler ⁵

Abstract

It has been assumed that the suprachiasmatic nucleus (SCN) synchronizes peripheral circadian oscillators. However, this has never been convincingly shown, since biochemical time series experiments are not feasible in behaviorally arrhythmic animals. By using long-term bioluminescence recording in freely moving mice, we show that the SCN is indeed required for maintaining synchrony between organs. Surprisingly, however, circadian oscillations persist in the livers of mice devoid of an SCN or oscillators in cells other than hepatocytes. Hence, similar to SCN neurons, hepatocytes can maintain phase coherence in the absence of Zeitgeber signals produced by other organs or environmental cycles.

Keywords: circadian gene expression; in vivo bioluminescence recording; liver; suprachiasmatic nucleus.

• PMID: 33602874
• DOI: 10.1101/gad.346460.120

Curr Top Dev Biol. 2020;140:209-254. doi: 10.1016/bs.ctdb.2020.02.002. Epub 2020 Feb 26.

From mother to embryo: A molecular perspective on zygotic genome activation

Edlyn Wu ¹, Nadine L Vastenhouw ²Affiliations expand

Abstract

In animals, the early embryo is mostly transcriptionally silent and development is fueled by maternally supplied mRNAs and proteins. These maternal products are important not only for survival, but also to gear up the zygote’s genome for activation. Over the last three decades, research with different model organisms and experimental approaches has identified molecular factors and proposed mechanisms for how the embryo transitions from being transcriptionally silent to transcriptionally competent. In this chapter, we discuss the molecular players that shape the molecular landscape of ZGA and provide insights into their mode of action in activating the transcription program in the developing embryo.

Keywords: Chromatin; Embryo development; Maternal-to-zygotic transition; Nuclear organization; Pioneer factors; Transcription factors; Transcriptional regulation; Zygotic genome activation.

• PMID: 32591075
• DOI: 10.1016/bs.ctdb.2020.02.002