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Sisu Han, Daniel J Dennis, Anjali Balakrishnan, Rajiv Dixit, Olivier Britz, Dawn Zinyk, Yacine Touahri, Thomas Olender, Marjorie Brand, François Guillemot, Deborah Kurrasch, Carol Schuurmans
Neural progenitors undergo temporal identity transitions to sequentially generate the neuronal and glial cells that make up the mature brain. Proneural genes have well characterized roles in promoting neural cell differentiation and subtype specification, but they also regulate the timing of identity transitions through poorly understood mechanisms. Here we investigated how the highly-related proneural genes Neurog1 and Neurog2 interact to control the timing of neocortical neurogenesis. We found that Neurog1 acts in an atypical fashion as it is required to suppress rather than promote neuronal differentiation in early corticogenesis...
September 10, 2018: Development
Aida Rodrigo Albors, Pamela A Halley, Kate G Storey
The vertebrate body forms by continuous generation of new tissue from progenitors at the posterior end of the embryo. The study of these axial progenitors has proved challenging in vivo largely due to the lack of unique molecular markers to identify them. Here, we elucidate the expression pattern of the transcription factor Nkx1-2 in the mouse embryo and show that it identifies axial progenitors throughout body axis elongation, including neuromesodermal progenitors and early neural and mesodermal progenitors...
September 10, 2018: Development
Ram P Kumar, Soma Ray, Pratik Home, Biswarup Saha, Bhaswati Bhattacharya, Heather M Wilkins, Hemantkumar Chavan, Avishek Ganguly, Jessica Milano-Foster, Arindam Paul, Partha Krishnamurthy, Russell H Swerdlow, Soumen Paul
Early mammalian development is critically dependent on the establishment of oxidative energy metabolism within the trophectoderm (TE) lineage. Unlike inner cell mass (ICM), TE cells enhance ATP production via mitochondrial oxidative phosphorylation (OXPHOS) and this metabolic preference is essential for blastocyst maturation. However, molecular mechanisms that regulate establishment of oxidative energy metabolism in TE cells are incompletely understood. Here, we show that conserved transcription factor TEAD4, which is essential for pre-implantation mammalian development, regulates this process by promoting mitochondrial transcription...
September 10, 2018: Development
Nora Gigli-Bisceglia, Timo Engelsdorf, Miroslav Strnad, Lauri Vaahtera, Ghazanfar Abbas Khan, Amel Jamoune, Leila Alipanah, Ondřej Novák, Staffan Persson, Jan Hejatko, Thorsten Hamann
During plant growth and defense, cell cycle activity needs to be coordinated with cell wall integrity. Little is known about how coordination is achieved. Here we investigated coordination in Arabidopsis thaliana seedlings by studying the impact of cell wall damage (CWD, caused by cellulose biosynthesis inhibition) on cytokinin homeostasis, cell cycle gene expression and shape in root tips. CWD inhibited cell cycle gene expression and increased transition zone cell width in an osmo-sensitive manner. These results were correlated with CWD-induced, osmo-sensitive changes in cytokinin homeostasis...
September 6, 2018: Development
Joseph H Shawky, Uma L Balakrishnan, Carsten Stuckenholz, Lance A Davidson
The large-scale movements that construct complex three-dimensional tissues during development are governed by universal physical principles. Fine-grained control of both mechanical properties and force production is critical to the successful placement of tissues and shaping of organs. Embryos of the frog Xenopus laevis provide a dramatic example of these physical processes, since dorsal tissues increase in Young's modulus by six-fold to 80 Pascal over eight hours as germ layers and the central nervous system are formed...
September 6, 2018: Development
Nayuta Yakushiji-Kaminatsui, Takashi Kondo, Ken-Ichi Hironaka, Jafar Sharif, Takaho A Endo, Manabu Nakayama, Osamu Masui, Yoko Koseki, Kaori Kondo, Osamu Ohara, Miguel Vidal, Yoshihiro Morishita, Haruhiko Koseki
Suppression of Meis genes in the distal limb bud is required for Proximal-Distal (PD) specification of the forelimb. Polycomb group (PcG) factors play a role in downregulation of retinoic acid (RA)-related signals in the distal forelimb bud, causing Meis repression. It is, however, not known if downregulation of RA-related signals and PcG-mediated proximal genes repression are functionally linked. Here, we reveal that PcG factors and RA-related signals antagonize each other to polarize Meis2 expression along the PD axis...
September 6, 2018: Development
Jingjing Sun, Angelike Stathopoulos
To support tissue and organ development, cells transition between epithelial and mesenchymal states. Here we investigated how mesoderm cells change state in Drosophila embryos and whether fibroblast growth factor (FGF) signaling plays a role. During gastrulation, presumptive mesoderm cells invaginate, undergo an epithelial-to-mesenchymal state transition (EMT) and migrate upon the ectoderm. Our data show that EMT is a prolonged process in which adherens junctions progressively decrease in number throughout the mesoderm cells' migration...
September 6, 2018: Development
Seth W Cheetham, Wolfram H Gruhn, Jelle van den Ameele, Robert Krautz, Tony D Southall, Toshihiro Kobayashi, M Azim Surani, Andrea H Brand
The precise control of gene expression by transcription factor networks is critical to organismal development. The predominant approach for mapping transcription factor-chromatin interactions has been chromatin immunoprecipitation (ChIP). However, ChIP requires a large number of homogeneous cells and antisera with high specificity. A second approach, DamID, has the drawback that high levels of Dam methylase are toxic. Here we modify our Targeted DamID approach (TaDa) to enable cell type-specific expression in mammalian systems, generating an inducible system (mammalian TaDa or MaTaDa) to identify protein/DNA interactions in 100 to 1000 times fewer cells than ChIP...
September 5, 2018: Development
Sung K Chiu, Jesslyn Saw, Yizhou Huang, Stefan E Sonderegger, Nicholas C Wong, David R Powell, Dominic Beck, John E Pimanda, Cedric S Tremblay, David J Curtis
Stem Cell Leukemia ( Scl or Tal1 ) and Lymphoblastic Leukemia 1 ( Lyl1 ) are highly related members of the basic helix-loop-helix (bHLH) family of transcription factors that are co- expressed in the erythroid lineage. Previous studies suggest that Scl is essential for primitive erythropoiesis. However, analysis of single-cell RNA-sequencing data of early embryos showed that primitive erythroid cells express both Scl and Lyl1 Therefore, to determine whether Lyl1 can function in primitive erythropoiesis, we crossed conditional Scl knockout mice with mice expressing a Cre recombinase under the control of the Epo receptor, active in erythroid progenitors...
September 5, 2018: Development
Stéphanie Backer, Ludmilla Lokmane, Camille Landragin, Marie Deck, Sonia Garel, Evelyne Bloch-Gallego
Trio, a member of the Dbl family of guanine nucleotide exchange factors (GEFs), activates Rac1 downstream of Netrin-1/DCC signalling in axon outgrowth and guidance. While it has been proposed that Trio also activates RhoA, the putative upstream factors remain unknown. Here, we show that Slit2 induces Trio-dependent RhoA activation, revealing a crosstalk between Slit and Trio/RhoA signalling. Consistently, we found that RhoA activity is hindered in vivo in trio mutant mouse embryos. We next studied the development of the ventral telencephalon and thalamocortical axons, previously shown to be controlled by Slit2...
September 3, 2018: Development
José Casal, Beatriz Ibáñez-Jiménez, Peter A Lawrence
Epithelial cells are polarised within the plane of the epithelium, forming oriented structures whose coordinated and consistent polarity (planar cell polarity, PCP) relates to the principal axes of the body or organ. In Drosophila at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the "core" or Stan/Fz system. Here we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Stan/Fz system...
August 28, 2018: Development
Richard Kaschula, Sofia Pinho, Claudio R Alonso
Disruptions of normal Hox gene expression can lead to severe morphological defects revealing a link between the regulation of Hox expression and pattern formation. Here we explore these links focusing on the impact of microRNA regulation on the expression of the Drosophila Hox gene Ultrabithorax ( Ubx ) during haltere development. Through the combination of bioinformatic and transcriptomic analyses we identify the miR-310/313 cluster ( miR-310C ) as a candidate regulator of Ubx Several experiments confirm this...
August 24, 2018: Development
Lele Li, Ge Tao, Matthew C Hill, Min Zhang, Yuka Morikawa, James F Martin
Loss of the paired-like homeodomain transcription factor 2 (Pitx2) in cardiomyocytes predisposes mice to atrial fibrillation and compromises neonatal regenerative capacity. Additionally, Pitx2 gain-of-function protects mature cardiomyocytes from ischemic injury and promotes heart repair. Here, we characterized the long-term myocardial phenotype after MI in Pitx2 conditional-knockout (Pitx2 CKO) mice. We found adipose-like tissue in Pitx2 CKO hearts 60 days after MI induced surgically at postnatal day 2 but not at day 8...
August 24, 2018: Development
Katie L Sinagoga, Heather A McCauley, Jorge O Múnera, Nichole A Reynolds, Jacob R Enriquez, Carey Watson, Hsiu-Chiung Yang, Michael A Helmrath, James M Wells
Enteroendocrine cells (EECs) are a minor cell population in the intestine yet they play a major role in digestion, satiety, and nutrient homeostasis. Recent development of human intestinal organoid models include EECs, but their rarity makes it difficult to study their formation and function. Here we used the EEC-inducting property of the transcription factor NEUROG3 in human pluripotent stem cell (PSC)-derived human intestinal organoids (HIOs) and colonic organoids (HCOs) to promote EEC development in vitro An 8 hour pulse of NEUROG3 expression induced expression of known target transcription factors and after 7 days organoids contained up to 25% EECs in the epithelium...
August 24, 2018: Development
Jiawei Sun, Lu Yan, Weimin Shen, Anming Meng
Maternal mRNAs and proteins dictate early embryonic development before zygotic genome activation. In the absence of transcription, elaborate control of maternal mRNA translation is of particular importance for oocyte maturation and early embryogenesis. By analyzing zebrafish ybx1 mutants with a null allele, we demonstrate an essential role of maternal ybx1 in repressing global translation in oocytes and embryos. Loss of maternal Ybx1 leads to impaired oocyte maturation and egg activation. Maternal ybx1 (M ybx1 ) mutant embryos fail to undergo normal cleavage and the maternal-to-zygotic transition (MZT)...
August 22, 2018: Development
Sera M Busse, Patrick T McMillen, Michael Levin
Regeneration of damaged body-parts requires coordination of size, shape, location, and orientation of tissue with the rest of the body. It is not currently known how far injury sites communicate with the remaining soma during repair, or what information may emanate from the injury site to other regions. We examined the bioelectric properties (resting potential gradients in the epidermis) of Xenopus froglets undergoing hind-limb amputation and observed that the contralateral (un-damaged) limb exhibits apparent depolarization signals immediately after the opposite hind-limb is amputated...
August 20, 2018: Development
Changgeng Peng, Alessandro Furlan, Ming-Dong Zhang, Jie Su, Moritz Lübke, Peter Lönnerberg, Hind Abdo, Jana Sontheimer, Erik Sundström, Patrik Ernfors
Touch and mechanical sensations require the development of several different kinds of sensory neurons dedicated to respond to certain types of mechanical stimuli. The transcription factor Shox2 (short stature homeobox 2) is involved in the generation of TRKB+ low-threshold mechanoreceptors (LTMRs), but mechanisms terminating this program and allowing for alternative fates are unknown. Here, we show that the conditional loss of miR-183-96-182 cluster leads to a failure of extinction of Shox2 during development and an increase in the proportion of Aδ LTMRs (TRKB+ /NECAB2+ ) neurons at the expense of Aβ slowly adapting (SA)-LTMRs (TRKC+ /Runx3- ) neurons...
August 20, 2018: Development
Hue M La, Ai-Leen Chan, Julien M D Legrand, Fernando J Rossello, Christina G Gangemi, Antonella Papa, Qiang Cheng, Eric F Morand, Robin M Hobbs
Male fertility is dependent on spermatogonial stem cells (SSCs) that self-renew and produce differentiating germ cells. Growth factors produced within the testis are essential for SSC maintenance but intrinsic factors dictating SSC response to these stimuli poorly characterised. Here we studied the role of GILZ, a TSC22D family protein and spermatogenesis regulator, in spermatogonial function and signalling. While broadly expressed in the germline, GILZ was prominent in undifferentiated spermatogonia and Gilz deletion in adults resulted in exhaustion of the GFRα1+ SSC-containing population and germline degeneration...
August 20, 2018: Development
Tomoyuki Furuya, Koro Hattori, Yoshitaka Kimori, Sakiko Ishida, Ryuichi Nishihama, Takayuki Kohchi, Hirokazu Tsukaya
Arabidopsis thaliana mutants deficient in ANGUSTIFOLIA (AN) exhibit several phenotypes at the sporophyte stage, such as narrow and thicker leaves, trichomes with two branches, and twisted fruits. It is thought that these phenotypes are caused by abnormal arrangement of cortical microtubules (MTs). AN homologs are present in the genomes of diverse land plants, including the basal land plant Marchantia polymorpha , and their molecular functions have been shown to be evolutionarily conserved in terms of the ability to complement the A...
August 20, 2018: Development
Eric D Bankaitis, Matthew E Bechard, Guoqiang Gu, Mark A Magnuson, Christopher V E Wright
During pancreas organogenesis, endocrine cells are born from progenitors residing in an epithelial plexus niche. After a period in a lineage-primed Neurog3 LO state, progenitors become endocrine-committed via upregulation of Neurog3 We find the Neurog3 LO to Neurog3 HI transition is associated with distinct stages of an epithelial egression process: narrowing the cell's apical surface, basalward cell movement, and eventual cell-rear detachment from the apical lumen surface to allow clustering as nascent islets under the basement membrane...
August 20, 2018: Development
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