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Monika Zmojdzian, Svetlana de Joussineau, Jean Philippe Da Ponte, Krzysztof Jagla
The Drosophila heart, composed of discrete subsets of cardioblasts and pericardial cells, undergoes Hox-triggered anterior-posterior morphogenesis, leading to a functional subdivision into heart proper and aorta, with its most anterior part forming a funnel-shaped cardiac outflow. Cardioblasts differentiate into Tin-positive 'working myocytes' and Svp-expressing ostial cells. However, developmental fates and functions of heart-associated pericardial cells remain elusive. Here we show that the pericardial cells that express transcription factor Even Skipped adopt distinct fates along the anterior-posterior axis...
December 15, 2017: Development
Pratik Narendra Pratap Singh, Upendra Singh Yadav, Kimi Azad, Pooja Goswami, Veena Kinare, Amitabha Bandyopadhyay
During appendicular skeletal development, the bi-potential cartilage anlagen gives rise to transient cartilage, which is eventually replaced by bone, and articular cartilage which caps the ends of individual skeletal elements. While the molecular mechanism that regulates transient cartilage differentiation is relatively better understood, the mechanism of articular cartilage differentiation has only begun to be unraveled. Further, the molecules that coordinate articular and transient cartilage differentiation processes are very poorly understood...
December 15, 2017: Development
Juan C Luna-Escalante, Pau Formosa-Jordan, Marta Ibañes
During metazoan development, Notch signaling drives spatially coordinated differentiation by establishing communication between adjacent cells. This occurs through either lateral inhibition, in which adjacent cells acquire distinct fates, or lateral induction, in which all cells become equivalent. Notch signaling is commonly activated by several distinct ligands, each of which drives signaling with a different efficiency upon binding to the Notch receptor of adjacent cells. Moreover, these ligands can also be distinctly regulated by Notch signaling...
December 14, 2017: Development
Eric Van Otterloo, Hong Li, Kenneth L Jones, Trevor Williams
The evolution of a hinged moveable jaw with variable morphology is considered a major factor behind the successful expansion of the vertebrates. DLX homeobox transcription factors are critical to establish the positional code that patterns the mandible, maxilla and intervening hinge domain, but how these genes are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2ɑ and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning. In the absence of these two genes the hinge domain is lost and there are alterations in the size and patterning of the jaws correlating with dysregulation of homeobox gene expression, with reduced levels of Emx, Msx and Dlx paralogs accompanied by an expansion of Six1...
December 11, 2017: Development
Geeta Godbole, Ashwin S Shetty, Achira Roy, Leora D'Souza, Bin Chen, Goichi Miyoshi, Gordon Fishell, Shubha Tole
During forebrain development, a telencephalic organizer called the cortical hem is critical for inducing hippocampal fate in adjacent cortical neuroepithelium. How the hem is restricted to its medial position is therefore a fundamental patterning question. Here, we demonstrate that Foxg1-Lhx2 interactions are critical for the formation of the hem. Loss of either gene causes a portion of the cortical neuroepithelium to transform into hem. We show that FOXG1 regulates Lhx2 expression in the cortical primordium...
December 11, 2017: Development
Sarah Rose C Garner, Monica C Castellanos, Katherine Baillie, Tianshun Lian, Douglas W Allan
Female-specific Ilp7 neuropeptide-expressing motoneurons (FS-Ilp7 motoneurons) are required in Drosophila for oviduct function in egg-laying. Here, we uncover cellular and genetic mechanisms underlying their female-specific generation. We demonstrate that programmed cell death (PCD) eliminates FS-Ilp7 motoneurons in males, and that this requires male-specific splicing of the sex determination gene fruitless (fru) into the FruMC isoform. However, in females, fru alleles that only generate FruM isoforms failed to kill FS-Ilp7 motoneurons...
December 11, 2017: Development
Zili Zhang, Wei Liu, Lingfeng Zhao, Zhibin Huang, Xiaohui Chen, Ning Ma, Jin Xu, Wenqing Zhang, Yiyue Zhang
T lymphocytes are key cellular components of acquired immune system and play essential roles in cell-mediated immunity. T cell development occurs in the thymus where 95% of immature thymocytes are eliminated via apoptosis. It is known that mutation of Zeb1, one of RB1 target genes, resulted in immature T cell decrease in mice. E2F1, an RB1 interacting protein, has been shown to regulate mature T cell development by interfering with thymocyte apoptosis. However, whether Rb1 regulate thymocyte development in vivo is still need to be further investigated...
December 11, 2017: Development
Frederik Ziebell, Sascha Dehler, Ana Martin-Villalba, Anna Marciniak-Czochra
New neurons are continuously generated in the dentate gyrus of the adult hippocampus. This continuous supply of newborn neurons is important to modulate cognitive functions. Yet, the number of newborn neurons declines with age. Increasing Wnt activity upon loss of the Dickkopf-1 can counteract both the decline of newborn neurons and the age-related cognitive decline. However, the precise cellular changes underlying the age-related decline or its rescue are fundamentally not understood. The present study combines a mathematical model and experimental data to address features controlling neural stem cell (NSC) dynamics...
December 11, 2017: Development
Sun-Hee Hwang, Kevin A White, Bandarigoda Nipunika Somatilaka, John M Shelton, James A Richardson, Saikat Mukhopadhyay
The role of basal suppression of Sonic hedgehog (Shh) pathway and its interaction with Indian hedgehog (Ihh) signaling during limb/skeletal morphogenesis is not well understood. The orphan G-protein-coupled receptor, Gpr161 localizes to primary cilia, and functions as a negative regulator of Shh signaling by promoting Gli transcriptional repressor versus activator formation. Here, we show that forelimb buds are not formed in Gpr161 knockout mice embryos despite establishment of prospective limb fields. Limb-specific deletion of Gpr161 resulted in prematurely expanded Shh signaling and ectopic Shh-dependent patterning defects to cause polysyndactyly...
December 8, 2017: Development
Patricia Murphy, Md Humayun Kabir, Tarini Srivastava, Michele E Mason, Chitra Umala Dewi, Seakcheng Lim, Andrian Yang, Djordje Djordjevic, Murray C Killingsworth, Joshua W K Ho, David G Harman, Michael D O'Connor
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells...
December 7, 2017: Development
Barbara Glöckle, Wojciech J Urban, Shiori Nagahara, Ellen D Andersen, Tetsuya Higashiyama, Paul E Grini, Arp Schnittger
After meiosis, an unequal cell division generates the male gamete lineage in flowering plants. The generative cell will undergo a second division, giving rise to the two gametes, i.e. the sperm cells. The other cell will develop into the vegetative cell that plays a crucial role in pollen tube formation and sperm delivery. Recently, the vegetative cell has been implicated to be important for programming of the chromatin state in sperm cells and/or the resulting fertilization products. Blocking the initial unequal division genetically, we first highlight that the default differentiation state after male meiosis is a vegetative fate consistent with earlier work...
December 7, 2017: Development
Yuka Kimura, Masao Tasaka, Keiko U Torii, Naoyuki Uchida
The epidermal cell layer and the tissues that lie underneath have different intrinsic functions during plant development. The stem cells within the shoot apical meristem (SAM) that give rise to aerial structures are located in the epidermal and internal tissue layers. However, our understanding of how the functions of these stem cells are coordinated across tissue layers so stem cells can behave as a single population remains limited. WUSCHEL (WUS) functions as a master regulator of stem cell activity. Here we show that loss of function in the ERECTA (ER)-family receptor kinase genes can rescue the mutant phenotype of wus plants (loss of stem cells), as demonstrated by the reinstated expression of a stem cell marker gene in the SAM epidermis...
December 7, 2017: Development
David Reichman, Laura Park, Limor Man, David Redmond, Kenny Chao, Richard P Harvey, Makoto M Taketo, Zev Rosenwaks, Daylon James
Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis (Naito et al., 2006; Qyang et al., 2007) and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSC) (Elliott et al., 2011; Iyer et al., 2016; Lian et al., 2012; Paige et al., 2010; Willems et al., 2011; Witty et al., 2014), however, few studies have investigated the role of Wnt signaling in specification of cardiac progenitor cells (CPC) toward downstream fates...
December 7, 2017: Development
Abigail S Tucker, Carlene J Dyer, Juan M Fons Romero, Tathyane H N Teshima, Jennifer C Fuchs, Hannah Thompson
The middle ear epithelium is derived from neural crest and endoderm, which line distinct regions of the middle ear cavity. Here we investigate the distribution of putative stem cell markers in the middle ear combined with an analysis of the location of label retaining cells (LRCs) to create a map of the middle ear mucosa. We show that proliferating cells and LRCs were associated with specific regions of the ear epithelium, concentrated in the hypotympanum at the base of the auditory bulla and around the ear drum...
December 7, 2017: Development
Alberto Joven, Heng Wang, Tiago Pinheiro, L Shahul Hameed, Laure Belnoue, András Simon
The overall bauplan of the tetrapod brain is highly conserved, yet significant variations exist among species in terms of brain size, structural composition and cellular diversity. Understanding processes underlying neural and behavioral development in a wide range of species is important both from an evolutionary developmental perspective as well as for the identification of cell sources with post-developmental neurogenic potential. Here we characterize germinal processes in the brain of Notophthalmus viridescens and Pleurodeles waltl during both development and adulthood...
December 7, 2017: Development
Villain Gaëlle, Poissonnier Loïc, Noueihed Baraa, Bonfils Gaëlle, Rivera Jose Carlos, Chemtob Sylvain, Soncin Fabrice, Mattot Virginie
MicroRNAs are key regulators of angiogenesis, as illustrated by the vascular defects observed in miR-126-deficient animals. While the miR-126 duplex gives rise to two mature microRNAs (miR-126-3p and -5p), these defects were attributed to the loss of miR-126-3p while the role of miR-126-5p during normal angiogenesis in vivo remains unknown. Here, we show that miR-126-5p is expressed in endothelial but also by retinal ganglion cells (RGC) of the postnatal retina and participates in protecting endothelial cells from apoptosis during the establishment of the retinal vasculature...
November 27, 2017: Development
Maria Sanz-Navarro, Kerstin Seidel, Zhao Sun, Ludivine Bertonnier-Brouty, Brad A Amendt, Ophir D Klein, Frederic Michon
In mice, the incisors grow throughout the animal's life, and this continuous renewal is driven by dental epithelial and mesenchymal stem cells. Sox2 is a principal marker of the epithelial stem cells that reside in the mouse incisor stem cell niche, called the labial cervical loop, but relatively little is known about the role of the Sox2+ stem cell population. In this study, we show that conditional deletion of Sox2 in the embryonic incisor epithelium leads to growth defects and impairment of ameloblast lineage commitment...
November 27, 2017: Development
Stefan Norlin, Vishal Parekh, Helena Edlund
Asna1, also known as TRC40, is implicated in delivery of tail anchored (TA) proteins into the ER, in vesicle-mediated transport, and in chaperoning unfolded proteins during oxidative stress/ATP depletion. We recently showed that Asna1 inactivation in β-cells resulted in impaired retrograde transport, ER stress and diabetes in mice. Here we show that Asna1 inactivation in pancreatic progenitor cells leads to redistribution of the Golgi TA SNAREs Syntaxin-5 and Syntaxin-6, Golgi fragmentation, and accumulation of cytosolic p62+ puncta...
November 27, 2017: Development
James A Gagnon, Kamal Obbad, Alexander F Schier
The role of the zebrafish transcription factor Nanog has been controversial. It has been suggested that Nanog is primarily required for the proper formation of the extraembryonic yolk syncytial layer (YSL) and only indirectly regulates gene expression in embryonic cells. In an alternative scenario, Nanog has been proposed to directly regulate transcription in embryonic cells during zygotic genome activation. To clarify the roles of Nanog, we performed a detailed analysis of zebrafish nanog mutants. While zygotic nanog mutants survive to adulthood, maternal-zygotic and maternal mutants exhibit developmental arrest at the blastula stage...
November 27, 2017: Development
Monika Saxena, Nitin Agnihotri, Jonaki Sen
Bone Morphogenetic Protein (BMP) signaling has been implicated in regulation of patterning of the forebrain and as a regulator of neurogenesis and gliogenesis in the mammalian cortex. However, its role in regulating other aspects of cortical development in vivo remains unexplored. We hypothesized that BMP signaling may regulate additional processes during the development of cortical neurons after observing the presence of active BMP signaling in a spatio-temporally dynamic pattern in the mouse cortex. Our investigation revealed that BMP signaling specifically regulates migration, polarity and the dendritic morphology of upper layer cortical neurons born at E15...
November 27, 2017: Development
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