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Eugene A Albert, Olga A Puretskaia, Nadezhda V Terekhanova, Anastasia Labudina, Christian Bökel
Niches have traditionally been characterized as signalling microenvironments that allow stem cells to maintain their fate. This definition implicitly assumes that the various niche signals are integrated towards a binary fate decision between stemness and differentiation. However, observations in multiple systems have demonstrated that stem cell properties such as proliferation and self renewal can be uncoupled at the level of niche signalling input, which is incompatible with this simplified view. We have studied the role of the transcriptional regulator Zfh1, a shared target of the Hedgehog and Jak/Stat niche signalling pathways, in the somatic stem cells of the Drosophila testis...
July 12, 2018: Development
Anjali Rao, Carole LaBonne
The Neural Crest, a progenitor population that drove vertebrate evolution, retains the broad developmental potential of the blastula cells it is derived from, even as neighboring cells undergo lineage-restriction. The mechanisms that enable these cells to preserve their developmental potential remain poorly understood. Here we explore the role that Histone Deacetylase (HDAC) activity plays in this process. We show that HDAC activity is essential for formation of neural crest, as well as for proper patterning of the early ectoderm...
July 12, 2018: Development
Selen Zülbahar, Florian Sieglitz, Rita Kottmeier, Benjamin Altenhein, Sebastian Rumpf, Christian Klämbt
During development tissue growth is mediated by either cell proliferation or cell growth, coupled with polyploidy. Both strategies are employed by the cell types comprising the Drosophila blood-brain barrier. During larval growth, the perineurial glia proliferate, whereas the subperineurial glia expand enormously and become polyploid. Here we show that the level of ploidy in subperineurial glia is controlled by the N-terminal asparagine amidohydrolase homolog Öbek, where high Öbek levels are required to limit replication...
July 12, 2018: Development
Eva S Liu, Janaina S Martins, Wanlin Zhang, Marie B Demay
The bone tendon attachment site known as the enthesis is comprised of a transitional zone between bone and tendon and plays an important role in enabling movement at this site. X-linked hypophosphatemia (XLH) is characterized by impaired activation of vitamin D, elevated serum FGF23 levels and low serum phosphate levels, which impair bone mineralization. Paradoxically, an important complication of XLH is mineralization of the enthesis (enthesopathy). Studies were undertaken to identify the cellular and molecular pathways important for normal post-natal enthesis maturation and to examine their role during the development of enthesopathy in mice with XLH (Hyp)...
July 12, 2018: Development
Takashi Iezaki, Kazuya Fukasawa, Tetsuhiro Horie, Gyujin Park, Samuel Robinson, Michio Nakaya, Hiroyuki Fujita, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Yukio Yoneda, Takashi Takarada, X Edward Guo, Hitoshi Kurose, Eiichi Hinoi
Extracellular signal-regulated kinase 5 (Erk5) belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by MAPK/Erk kinase-5 (Mek5), Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrated that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr249 , which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser206 in the linker region known to trigger its proteasomal degradation by Smurf1...
July 9, 2018: Development
Melissa A Metzler, Swetha Raja, Kelsey H Elliott, Regina M Friedl, Nhut Quang Huy Tran, Samantha A Brugmann, Melinda Larsen, Lisa L Sandell
In mammals, the epithelial tissues of major salivary glands generate saliva and drain it into the oral cavity. For submandibular salivary glands (SMG), it is known that the epithelial tissues arise during embryogenesis from naïve oral ectoderm adjacent to the base of the tongue, which begins to thicken, express SOX9, and invaginate into underlying mesenchyme. The developmental mechanisms initiating salivary gland development remain unexplored. In this study we show that retinoic acid (RA) signaling activity at the site of gland initiation is co-localized with expression of retinol metabolic genes Rdh10, and Aldh1a2 in the underlying SMG mesenchyme...
July 9, 2018: Development
Yamit Cohen-Tayar, Hadar Cohen, Yulia Mitiagin, Zohar Abarbanel, Carmit Levy, Masha Idelson, Benjamin Reubinoff, Shalev Itzkovitz, Shaul Raviv, Klaus Kaestner, Pablo Blinder, Ran Elkon, Ruth Ashery-Padan
The synchronized differentiation of neuronal and vascular tissues is crucial for normal organ development and function, although there is limited information about the mechanisms regulating the coordinated development of these tissues. The choroid vasculature of the eye serves as the main blood supply to the metabolically active photoreceptors, and develops together with the retinal pigmented epithelium (RPE). Here, we describe a novel regulatory relationship between the RPE transcription factors, Pax6 and Sox9 , which control the timing of RPE differentiation, and the adjacent choroid maturation...
July 9, 2018: Development
Bryan A Niedenberger, Kenneth Cook, Valentina Baena, Nicholas D Serra, Ellen K Velte, Julio E Agno, Karen A Litwa, Mark Terasaki, Brian P Hermann, Martin M Matzuk, Christopher B Geyer
Throughout the male reproductive lifespan, spermatogonial stem cells (SSCs) produce committed progenitors that proliferate and then remain physically connected in growing clones via short cylindrical intercellular bridges (ICBs). These ICBs, which enlarge in meiotic spermatocytes, have been demonstrated to provide a conduit for postmeiotic haploid spermatids to share sex chromosome-derived gene products. In addition to ICBs, spermatogonia exhibit multiple thin cytoplasmic projections. Here, we explored the nature of these projections, and found they are dynamic, span considerable distances from their cell body (≥25µm), either terminate or physically connect multiple adjacent spermatogonia, and allow for sharing of macromolecules...
July 6, 2018: Development
Luke R Baker, Bonnie M Weasner, Athena Nagel, Sarah D Neuman, Arash Bashirullah, Justin P Kumar
The Pax6 transcription factor is considered the master control gene for eye formation because (1) it is present within the genomes and retina/lens in all seeing animals; (2) severe retinal defects accompany its loss; (2) Pax6 genes have the ability to substitute for one another across the animal kingdom; and (4) Pax6 genes are capable of inducing ectopic eye/lens in flies and mammals. Many roles of Pax6 were first elucidated in Drosophila through studies of the gene eyeless ( ey ), which controls both growth of the entire eye-antennal imaginal disc and fate specification of the eye...
July 6, 2018: Development
Christian Ghiglione, Patrick Jouandin, Delphine Cérézo, Stéphane Noselli
Understanding how different cell types acquire their motile behaviour is central to many normal and pathological processes. Drosophila border cells represent a powerful model to address this question and to specifically decipher the mechanisms controlling collective cell migration. Here, we identify the Drosophila Insulin/Insulin-like growth factor Signalling (IIS) pathway as a key regulator controlling actin dynamics in border cells, independently of its function in growth control. Loss of IIS activity blocks the formation of actin-rich long cellular extensions that are important for the delamination and the migration of the invasive cluster...
July 6, 2018: Development
Joshua R York, Tian Yuan, Olga Lakiza, David W McCauley
The origin of the vertebrate head is one of the great unresolved issues in vertebrate evolutionary-developmental biology. Although many of the novelties in the vertebrate head and pharynx are derived from the neural crest, it is still unknown how early vertebrates patterned the neural crest within the ancestral body plan they inherited from invertebrate chordates. Here, using a basal vertebrate, the sea lamprey, we show that homologues of Semaphorin3F ligand and its Neuropilin receptors show complementary and dynamic patterns of expression that correlate with key periods of neural crest development (migration, patterning of cranial neural crest-derived structures)...
July 6, 2018: Development
H Ono, D Koop, L Z Holland
The larval pharynx of the cephalochordate Branchiostoma (amphioxus) is asymmetrical. The mouth is on the left and endostyle and gill slits are on the right. At the neurula, Nodal and Hedgehog ( Hh ) expression becomes restricted to the left. To dissect their respective roles in gill slit formation, we inhibited each pathway separately for 20 min at intervals during the neurula stage, before gill slits penetrate, and monitored effects on morphology and expression of pharyngeal markers. The results pinpoint the short interval spanning the gastrula/neurula transition as the critical period for specification and positioning of future gill slits...
July 6, 2018: Development
Marketa Pernisova, Martina Grochova, Tomas Konecny, Lenka Plackova, Danka Harustiakova, Tatsuo Kakimoto, Marcus G Heisler, Ondrej Novak, Jan Hejatko
Mutual interactions of the phytohormones cytokinins and auxin determine root or shoot identity during postembryonic de novo organogenesis in plants. However, our understanding to the role of hormonal metabolism and perception during early stages of cell fate reprograming is still elusive.In the hypocotyl explant assay, auxin activated root formation while cytokinins mediated early loss of the root identity, primordia disorganization and initiation of shoot development. Exogenous but also endogenous cytokinins influenced the initiation of newly formed organs as well as the pace of organ developmental sequence...
July 2, 2018: Development
Zhejun Xu, Qifei Liang, Xiaolei Song, Zhuangzhi Zhang, Susan Lindtner, Zhenmeiyu Li, Yan Wen, Guoping Liu, Teng Guo, Dashi Qi, Min Wang, Chunyang Wang, Hao Li, Yan You, Xin Wang, Bin Chen, Hua Feng, John L Rubenstein, Zhengang Yang
Dopamine receptor Drd1-expressing medium spiny neurons (D1 MSNs) and dopamine receptor Drd2-expressing medium spiny neurons (D2 MSNs) are the principal projection neurons in the striatum, including in the dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle) that are generated by the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the Sp8 and Sp9 transcription factors (TFs) selectively lose virtually all D2 MSNs due to reduced neurogenesis in the LGE, whereas Drd1 MSNs are largely unaffected...
July 2, 2018: Development
Aditi Sharma, Sudipta Halder, Martina Felix, Khairun Nisaa, Girish Deshpande, Mohit Prasad
As collective cell migration is intimately involved in different aspects of metazoan development, molecular mechanisms underlying this process are being explored in a variety of developmental contexts. Border cell (BC) migration during Drosophila oogenesis has emerged as an excellent genetic model for studying collective cell migration. BCs are of epithelial origin but acquire partial mesenchymal characteristics before migrating as a group towards the oocyte. Here we report that insulin signalling modulates collective BC movement during Drosophila oogenesis...
June 27, 2018: Development
Takanori Wakatake, Satoko Yoshida, Ken Shirasu
The haustorium in parasitic plants is an organ specialized for invasion and nutrient uptake from host plant tissues. Despite its importance, the developmental processes of haustoria are mostly unknown. To understand the dynamics of cell fate change and cellular lineage during the haustorium development, we performed live imaging-based marker expression analysis and cell-lineage tracing during haustorium formation in the model facultative root parasite Phtheirospermum japonicum Our live-imaging analysis revealed that haustorium formation was associated with induction of simultaneous cell division in multiple cellular layers such as epidermis, cortex, and endodermis...
June 27, 2018: Development
Jinwoo Seong, Nam-Shik Kim, Jee-Ah Kim, Wonbin Lee, Ji-Yun Seo, Min Kyu Yum, Ji-Hoon Kim, Inkuk Park, Jong-Seol Kang, Sung-Hwan Bae, Cheol-Heui Yun, Young-Yun Kong
Mammary glands develop through primary ductal elongation and side branching to maximize the spatial area. Although primary ducts are generated by bifurcation of terminal end buds, the mechanism through which side branching occurs is still largely unclear. Here, we show that inhibitor of DNA-binding 2 (ID2) drives side branch formation through differentiation of K6+ bipotent progenitor cells into CD61+ luminal progenitor cells. Id2 -null mice had side branching defects, along with developmental blockage of K6+ bipotent progenitor cells into CD61+ luminal progenitor cells...
June 27, 2018: Development
Emily Abrash, M Ximena Anleu Gil, Juliana L Matos, Dominique C Bergmann
All multicellular organisms must properly pattern cell types to generate functional tissues and organs. The organized and predictable cell lineages of the Brachypodium leaf enabled us to characterize the role of the MAPK kinase kinase gene BdYODA1 in regulating asymmetric cell divisions. We find that YODA genes promote normal stomatal spacing patterns in both Arabidopsis and Brachypodium , despite species-specific differences in those patterns. Using lineage tracing and cell fate markers, we show that, unexpectedly, patterning defects in bdyoda1 mutants do not arise from faulty physical asymmetry in cell divisions but rather from improper enforcement of alternative cellular fates after division...
June 26, 2018: Development
Uma M Neelathi, Damian Dalle Nogare, Ajay B Chitnis
The zebrafish posterior Lateral Line primordium migrates along a path, defined by the chemokine Cxcl12a, periodically depositing neuromasts, to pioneer formation of the zebrafish posterior Lateral Line system. snail1b , known for its role in promoting cell migration, is expressed in leading cells of the primordium in response to Cxcl12a, while its expression in trailing cells is inhibited by Fgf signaling. snail1b knockdown delays initiation of primordium migration. This delay is associated with aberrant expansion of epithelial cell adhesion molecule ( epcam ) and reduction of cadherin2 expression in a leading part of the primordium...
June 26, 2018: Development
Moritz Sander, Teresa Eichenlaub, Héctor Herranz
Tissue growth has to be carefully controlled to generate well-functioning organs. microRNAs are small noncoding RNAs that modulate the activity of target genes and play a pivotal role in animal development. Understanding the functions of microRNAs in development requires the identification of their target genes. Here, we find that the conserved microRNA miR-8/miR-200 controls tissue growth and homeostasis in the Drosophila wing imaginal disc. Upregulation of miR-8 causes the repression of Yorkie , the effector of the Hippo pathway in Drosophila , and reduces tissue size...
June 26, 2018: Development
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