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Genesis: the Journal of Genetics and Development

Jermaine Ross, Alexander Kuzin, Thomas Brody, Ward F Odenwald
While developmental studies of Drosophila neural stem cell lineages have identified transcription factors (TFs) important to cell identity decisions, currently only an incomplete understanding exists of the cis-regulatory elements that control the dynamic expression of these TFs. Our previous studies have identified multiple enhancers that regulate the POU-domain TF paralogs nubbin and pdm-2 genes. Evolutionary comparative analysis of these enhancers reveals that they each contain multiple conserved sequence blocks (CSBs) that span TF DNA-binding sites for known regulators of neuroblast (NB) gene expression in addition to novel sequences...
July 13, 2018: Genesis: the Journal of Genetics and Development
Lan Hai, Maria M Szwarc, Margeaux Wetendorf, San-Pin Wu, Mary C Peavey, Sandra L Grimm, Dean P Edwards, Francesco J DeMayo, John P Lydon
Using a Rosa26 gene targeting strategy in mouse embryonic stem cells, we have generated a new transgenic mouse (Pgr-BLSL ), which is designed to conditionally express the epitope-tagged mouse progesterone receptor-B (PGR-B) isoform when crossed with a specific cre driver mouse. To functionally validate this transgenic mouse, we crossed the Pgr-BLSL mouse with the MMTV-CREA transgenic mouse to create the MMTV-CREA/Pgr-BLSL bigenic (termed PR-B:OE to denote PGR-B overexpressor). As expected, transgene-derived PGR-B protein was specifically targeted to the virgin mammary gland epithelium...
July 13, 2018: Genesis: the Journal of Genetics and Development
Sriivatsan G Rajan, Kristin L Gallik, James R Monaghan, Rosa A Uribe, Marianne E Bronner, Ankur Saxena
Analysis of cell cycle entry/exit and progression can provide fundamental insights into stem cell propagation, maintenance, and differentiation. The neural crest is a unique stem cell population in vertebrate embryos that undergoes long-distance collective migration and differentiation into a wide variety of derivatives. Using traditional techniques such as immunohistochemistry to track cell cycle changes in such a dynamic population is challenging, as static time points provide an incomplete spatiotemporal picture...
June 28, 2018: Genesis: the Journal of Genetics and Development
Staci E Engle, Patrick J Antonellis, Logan S Whitehouse, Ruchi Bansal, Michelle R Emond, James D Jontes, Robert A Kesterson, Kirk Mykytyn, Nicolas F Berbari
The neuropeptide, melanin concentrating hormone (MCH), and its G protein-coupled receptor, melanin concentrating hormone receptor 1 (Mchr1), are expressed centrally in adult rodents. MCH signaling has been implicated in diverse behaviors such as feeding, sleep, anxiety, as well as addiction and reward. While a model utilizing the Mchr1 promoter to drive constitutive expression of Cre recombinase (Mchr1-Cre) exists, there is a need for an inducible Mchr1-Cre to determine the roles for this signaling pathway in neural development and adult neuronal function...
May 27, 2018: Genesis: the Journal of Genetics and Development
Nadège Gouignard, Cyril Andrieu, Eric Theveneau
Neural crest (NC) cells were described for the first time in 1868 by Wilhelm His. Since then, this amazing population of migratory stem cells has been intensively studied. It took a century to fully unravel their incredible abilities to contribute to nearly every organ of the body. Yet, our understanding of the cell and molecular mechanisms controlling their migration is far from complete. In this review, we summarize the current knowledge on epithelial-mesenchymal transition and collective behavior of NC cells and propose further stops at which the NC train might be calling in the near future...
April 20, 2018: Genesis: the Journal of Genetics and Development
Olga Ossipova, Ryan Kerney, Jean-Pierre Saint-Jeannet, Sergei Y Sokol
The neural crest (NC) multipotent progenitor cells form at the neural plate border and migrate to diverse locations in the embryo to differentiate into many cell types. NC is specified by several embryonic pathways, however the role of noncanonical Wnt signaling in this process remains poorly defined. Daam1 is a formin family protein that is present in embryonic ectoderm at the time of NC formation and can mediate noncanonical Wnt signaling. Our interference experiments indicated that Daam1 is required for NC gene activation...
April 19, 2018: Genesis: the Journal of Genetics and Development
Julien Debbache, Vadims Parfejevs, Lukas Sommer
The neural crest is one of the embryonic structures with the broadest developmental potential in vertebrates. Morphologically, neural crest cells emerge during neurulation in the dorsal folds of the neural tube before undergoing an epithelial-to-mesenchymal transition (EMT), delaminating from the neural tube, and migrating to multiple sites in the growing embryo. Neural crest cells generate cell types as diverse as peripheral neurons and glia, melanocytes, and so-called mesectodermal derivatives that include craniofacial bone and cartilage and smooth muscle cells in cardiovascular structures...
April 19, 2018: Genesis: the Journal of Genetics and Development
Sandra Acosta, Luciano Fiore, Isabel Anna Carota, Guillermo Oliver
Targeted genome editing in mouse embryonic stem cells (ESCs) is a powerful resource to functionally characterize genes and regulatory elements. The use of the CRISPR/Cas9 genome editing approach has remarkably improved the time and efficiency of targeted recombination. However, the efficiency of this protocol is still far from ideal when aiming for bi-allelic homologous recombination, requiring at least two independent targeting recombination events. Here we describe an improved protocol that uses two gRNAs flanking the selected targeted region, leading to highly efficient homologous recombination in mouse ESCs...
May 2018: Genesis: the Journal of Genetics and Development
Elaine Emmerson, Sarah M Knox
Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by autoimmune diseases such as Sjögren's syndrome. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. However, these approaches have been hampered by a lack of knowledge on the identity of salivary stem cell populations and their regulators...
May 2018: Genesis: the Journal of Genetics and Development
Tsuyoshi Tokusumi, Yumiko Tokusumi, Robert A Schulz
Hedgehog (Hh) pathway signaling is crucial for the maintenance of blood cell progenitors in the lymph gland hematopoietic organ present in Drosophila third instar larvae. Previous studies from our lab have likewise shown the importance of the mir-7 and bag of marbles (bam) genes in maintaining the progenitor state. Thus, we sought to investigate a possible interaction between the Hh pathway and mir-7/bam in the prohemocyte population within this hematopoietic tissue. Gain of function mir-7 was able to rescue a blood cell progenitor depletion phenotype caused by Patched (Ptc) inhibition of Hh pathway signaling in these cells...
May 2018: Genesis: the Journal of Genetics and Development
Patricia Abete-Luzi, David M Eisenmann
The cuticle, the outer covering of the nematode C. elegans, is synthesized five times during the worm's life by the underlying hypodermis. Cuticle collagens, the major cuticle component, are encoded by a large family of col genes and, interestingly, many of these genes express predominantly at a single developmental stage. This temporal preference motivated us to investigate the mechanisms underlying col gene expression and here we focus on a subset of col genes expressed in the L4 stage. We identified minimal promoter regions of <300 bp for col-38, col-49, and col-63...
May 2018: Genesis: the Journal of Genetics and Development
Janine M Ziermann, Rui Diogo, Drew M Noden
Patterning of craniofacial muscles overtly begins with the activation of lineage-specific markers at precise, evolutionarily conserved locations within prechordal, lateral, and both unsegmented and somitic paraxial mesoderm populations. Although these initial programming events occur without influence of neural crest cells, the subsequent movements and differentiation stages of most head muscles are neural crest-dependent. Incorporating both descriptive and experimental studies, this review examines each stage of myogenesis up through the formation of attachments to their skeletal partners...
April 16, 2018: Genesis: the Journal of Genetics and Development
Brian K Hall
Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural folds have since been shown to differentiate into almost two dozen vertebrate cell types and to have played major roles in the evolution of such vertebrate features as bone, jaws, teeth, visceral (pharyngeal) arches, and sense organs. I discuss the discovery that ectodermal neural crest gave rise to mesenchyme and the controversy generated by that finding; the germ layer theory maintained that only mesoderm could give rise to mesenchyme...
April 10, 2018: Genesis: the Journal of Genetics and Development
Gonzalo Aparicio, Cristina Arruti, Flavio R Zolessi
Neurulation involves a complex coordination of cellular movements that are in great part based on the modulation of the actin cytoskeleton. MARCKS, an F-actin-binding protein and the major substrate for PKC, is necessary for gastrulation and neurulation morphogenetic movements in mice, frogs, and fish. We previously showed that this protein accumulates at the apical region of the closing neural plate in chick embryos, and here further explore its role in this process and how it is regulated by PKC phosphorylation...
April 2018: Genesis: the Journal of Genetics and Development
Hyea Jin Gil, Wanshu Ma, Guillermo Oliver
The lymphatic vascular system is a one-direction network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells responsible for maintaining fluid homeostasis. Some of the main functions of the lymphatic vasculature are to drain fluid from the extracellular spaces and return it back to the blood circulation, lipid absorption from the intestinal tract, and transport of immune cells to lymphoid organs. A number of genes controlling the development of the mammalian lymphatic vasculature have been identified in the last few years, and their functional roles started to be characterized using gene inactivation approaches in mice...
April 2018: Genesis: the Journal of Genetics and Development
Shuangbo Kong, Guixian Liang, Zhaowei Tu, Dunjin Chen, Haibin Wang, Jinhua Lu
Placental development is a complex and highly controlled process during which trophoblast stem cells differentiate to various trophoblast subtypes. The early embryonic death of systemic gene knockout models hampers the investigation of these genes that might play important roles during placentation. A trophoblast specific Cre mouse model would be of great help for dissecting out the potential roles of these genes during placental development. For this purpose, we generate a transgenic mouse with the Cre recombinase inserted into the endogenous locus of Elf5 gene that is expressed specifically in placental trophoblast cells...
April 2018: Genesis: the Journal of Genetics and Development
Mei Xu, Xiaoling Xie, Xuhui Dong, Guoqing Liang, Lin Gan
LHX3, a LIM-homeodomain transcription factor, is broadly expressed in the developing pituitary, spinal cord, medulla, retina and inner ear, and plays essential roles during embryonic development. Mice with homozygous Lhx3 null mutation exhibit failure in the formation of pituitary gland and die perinatally. To facilitate the functional study of Lhx3 in mice, we engineered and characterized two novel Lhx3 mouse strains: Lhx3GFP reporter knock-in and Lhx3loxP conditional knockout mice. Coimmunolabeling of LHX3 and GFP shows that the expression pattern of the knock-in GFP reporter recapitulates that of endogenous LHX3 in cochlea, vestibule, retina, and spinal cord...
April 2018: Genesis: the Journal of Genetics and Development
Tomoko Matsuzaki, Huan Wang, Yukio Imamura, Shunya Kondo, Shuichiro Ogawa, Makoto Noda
Reck encodes a membrane-anchored glycoprotein implicated in the regulation of extracellular metalloproteinases, Notch-signaling, and Wnt7-signaling and shown to play critical roles in embryogenesis and tumor suppression. Precise mechanisms of its actions in vivo, however, remain largely unknown. By homologous recombination, we generated a new Reck allele, ReckCreERT2 (MGI symbol: Reck<tm3.1(cre/ERT2)Noda>). This allele is defective in terms of Reck function but expected to induce loxP-mediated recombination in the cells committed to express Reck...
April 2018: Genesis: the Journal of Genetics and Development
Lexy M Kindt, Alicia R Coughlin, Tianna R Perosino, Haley N Ersfeld, Marshall Hampton, Jennifer O Liang
Anencephaly is a fatal human neural tube defect (NTD) in which the anterior neural tube remains open. Zebrafish embryos with reduced Nodal signaling display an open anterior neural tube phenotype that is analogous to anencephaly. Previous work from our laboratory suggests that Nodal signaling acts through induction of the head mesendoderm and mesoderm. Head mesendoderm/mesoderm then, through an unknown mechanism, promotes formation of the polarized neuroepithelium that is capable of undergoing the movements required for closure...
March 2018: Genesis: the Journal of Genetics and Development
Alexander Kuzin, Svetlana Smith, Thomas Brody, Ward F Odenwald
Evolutionary analysis of cis-regulatory DNA reveals that enhancers consist of clusters of conserved sequence blocks (CSBs) that are made up of both unique and repeated sequence elements. This study seeks to address the basis for spatial and temporal regulation of neuroblas. A search for temporally restricted CNS NB enhancers identified one within the transcription factor grainyhead (grh) gene locus. The intronic enhancer, grh-15, contains two separable semi-autonomous activities, one that drives expression predominantly within the developing brain NBs and another in ventral cord NBs...
March 2018: Genesis: the Journal of Genetics and Development
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