TY  - JOUR
AB  - We previously demonstrated that long-term trained immunity (TRIM) involves adaptations that imprint innate immune memory in long-lived myelopoiesis precursors and their progeny, monocytes/macrophages and neutrophils, which thereby acquire enhanced responsiveness to future challenges. Here, we show that a distinct component of myeloid biology, osteoclastogenesis, can also undergo innate immune training. Indeed, β-glucan-induced TRIM was associated with an increased osteoclastogenesis bias in the bone marrow and an expansion of monocytes/osteoclast progenitors in the periphery, resulting in aggravated severity of experimental periodontitis and arthritis. In the setting of trained inflammatory osteoclastogenesis, we observed transcriptomic rewiring in synovial myeloid cells of arthritic mice, featuring prominent upregulation of the transcription factor melanogenesis-associated transcription factor (MITF). Adoptive transfer of splenic monocytes from β-glucan-trained mice to naive recipients exacerbated arthritis in the latter in a strictly MITF-dependent manner. Our findings establish trained osteoclastogenesis as a maladaptive component of TRIM and potentially provide therapeutic targets in inflammatory bone loss disorders.
AU  - Haacke, N.*
AU  - Wang, H.*
AU  - Yan, S.*
AU  - Barovic, M.*
AU  - Li, X.*
AU  - Nagai, K.*
AU  - Botezatu, A.*
AU  - Hatzioannou, A.*
AU  - Gercken, B.*
AU  - Trimaglio, G.*
AU  - Shah, A.U.*
AU  - Wang, J.*
AU  - Ye, L.*
AU  - Jaykar, M.T.*
AU  - Rauner, M.*
AU  - Wielockx, B.*
AU  - Chung, K.J.*
AU  - Netea, M.G.*
AU  - Kalafati, L.*
AU  - Hajishengallis, G.*
AU  - Chavakis, T.
C1  - 73554
C2  - 57097
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1854-1870
TI  - Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice.
JO  - Dev. Cell
VL  - 60
IS  - 13
PB  - Cell Press
PY  - 2025
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Cells must duplicate their genome before they divide to ensure equal transmission of genetic information. The genome is replicated with a defined temporal order, replication timing (RT), which is cell-type specific and linked to 3D-genome organization. During mammalian development, RT is initially not well defined and becomes progressively consolidated from the 4-cell stage. However, the molecular regulators are unknown. Here, by combining loss-of-function analysis with genome-wide investigation of RT in mouse embryos, we identify Rap1 interacting factor 1 (RIF1) as a regulator of the progressive consolidation of RT. Embryos without RIF1 show DNA replication features of an early, more totipotent state. RIF1 regulates the progressive stratification of RT values and its depletion leads to global RT changes and a more heterogeneous RT program. Developmental RT changes are disentangled from changes in transcription and nuclear organization, specifically nuclear lamina association. Our work provides molecular understanding of replication and genome organization at the beginning of mammalian development.
AU  - Nakatani, T.
AU  - Schauer, T.
AU  - Pal, M.
AU  - Ettinger, A.
AU  - Altamirano-Pacheco, L.
AU  - Zorn, J.
AU  - Gilbert, D.M.*
AU  - Torres-Padilla, M.E.
C1  - 74170
C2  - 57102
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 2149-2162
TI  - RIF1 controls replication timing in early mouse embryos independently of lamina-associated nuclear organization.
JO  - Dev. Cell
VL  - 60
IS  - 16
PB  - Cell Press
PY  - 2025
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - A central question in cell and developmental biology is how extracellular cues control the differentiation of multipotent progenitors in a dynamically changing niche. Here, we identify apical-basal polarity as the main regulator of the differentiation of multipotent pancreatic Neurogenin3+ endocrine progenitors (EPs) into the beta or alpha cell fates. We show that human EPs dynamically change their apical-basal polarity status. Whereas polarized EPs are predisposed to differentiate into beta cells rather than alpha cells, inhibiting apical-basal polarity selectively suppresses beta cell differentiation. Single-cell RNA sequencing and complementary mechanistic data demonstrate that apical-basal polarity in human EPs promotes beta cell specification via cyclic AMP (cAMP)/PKA-cAMP response element binding protein (CREB)-EGR1-mediated inhibition of ARX expression, while reduced cAMP levels in non-polarized human EPs maintain expression of ARX, leading to alpha cell differentiation. These findings identify the apical-basal polarity status of multipotent EPs as a critical epithelial feature that determines their fate into the alpha or beta cell lineages.
AU  - Tiemann, U.*
AU  - Tian, C.
AU  - Hermann, F.*
AU  - Proks, M.*
AU  - Skovgaard, E.*
AU  - Kulik, I.
AU  - Di, Y.
AU  - Sedzinski, J.*
AU  - Semb, H.
C1  - 73632
C2  - 57147
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1871-1883.e5
TI  - Pancreatic alpha and beta cell fate choice is directed by apical-basal polarity dynamics.
JO  - Dev. Cell
VL  - 60
IS  - 13
PB  - Cell Press
PY  - 2025
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - A classical question in biology is how different processes are controlled in space and time, with research pointing to different mechanisms as timers. In this collection of Voices, we asked researchers to define their scientific questions related to time-keeping and the approaches they use to answer them.
AU  - Ebisuya, M.*
AU  - Rayon, T.*
AU  - Diaz-Cuadros, M.*
AU  - Chalut, K.J.*
AU  - Wu, G.*
AU  - Dodd, A.N.*
AU  - Torres-Padilla, M.E.
AU  - Levine, M.E.*
AU  - Gladyshev, V.N.*
C1  - 71331
C2  - 56044
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1623-1627
TI  - Understanding how cells and organisms keep time during development.
JO  - Dev. Cell
VL  - 59
IS  - 13
PB  - Cell Press
PY  - 2024
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The anterior visceral endoderm (AVE) differs from the surrounding visceral endoderm (VE) in its migratory behavior and ability to restrict primitive streak formation to the opposite side of the mouse embryo. To characterize the molecular bases for the unique properties of the AVE, we combined single-cell RNA sequencing of the VE prior to and during AVE migration with phosphoproteomics, high-resolution live-imaging, and short-term lineage labeling and intervention. This identified the transient nature of the AVE with attenuation of "anteriorizing" gene expression as cells migrate and the emergence of heterogeneities in transcriptional states relative to the AVE's position. Using cell communication analysis, we identified the requirement of semaphorin signaling for normal AVE migration. Lattice light-sheet microscopy showed that Sema6D mutants have abnormalities in basal projections and migration speed. These findings point to a tight coupling between transcriptional state and position of the AVE and identify molecular controllers of AVE migration.
AU  - Thowfeequ, S.*
AU  - Fiorentino, J.
AU  - Hu, D.*
AU  - Solovey, M.
AU  - Ruane, S.*
AU  - Whitehead, M.*
AU  - Zhou, F.*
AU  - Godwin, J.*
AU  - Mateo-Otero, Y.*
AU  - Vanhaesebroeck, B.*
AU  - Scialdone, A.
AU  - Srinivas, S.*
C1  - 70813
C2  - 55753
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 2347-2363.e9
TI  - An integrated approach identifies the molecular underpinnings of murine anterior visceral endoderm migration.
JO  - Dev. Cell
VL  - 59
IS  - 17
PB  - Cell Press
PY  - 2024
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Acute brain injuries evoke various response cascades directing the formation of the glial scar. Here, we report that acute lesions associated with hemorrhagic injuries trigger a re-programming of oligodendrocytes. Single-cell RNA sequencing highlighted a subpopulation of oligodendrocytes activating astroglial genes after acute brain injuries. By using PLP-DsRed1/GFAP-EGFP and PLP-EGFPmem/GFAP-mRFP1 transgenic mice, we visualized this population of oligodendrocytes that we termed AO cells based on their concomitant activity of astro- and oligodendroglial genes. By fate mapping using PLP- and GFAP-split Cre complementation and repeated chronic in vivo imaging with two-photon laser-scanning microscopy, we observed the conversion of oligodendrocytes into astrocytes via the AO cell stage. Such conversion was promoted by local injection of IL-6 and was diminished by IL-6 receptor-neutralizing antibody as well as by inhibiting microglial activation with minocycline. In summary, our findings highlight the plastic potential of oligodendrocytes in acute brain trauma due to microglia-derived IL-6.
AU  - Bai, X.*
AU  - Zhao, N.*
AU  - Koupourtidou, C.
AU  - Fang, L.P.*
AU  - Schwarz, V.
AU  - Caudal, L.C.*
AU  - Zhao, R.*
AU  - Hirrlinger, J.*
AU  - Walz, W.*
AU  - Bian, S.*
AU  - Huang, W.*
AU  - Ninkovic, J.
AU  - Kirchhoff, F.*
AU  - Scheller, A.*
C1  - 67905
C2  - 54383
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1153-1169.e5
TI  - In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury.
JO  - Dev. Cell
VL  - 58
IS  - 13
PB  - Cell Press
PY  - 2023
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Basic helix-loop-helix genes, particularly proneural genes, are well-described triggers of cell differentiation, yet information on their dynamics is limited, notably in human development. Here, we focus on Neurogenin 3 (NEUROG3), which is crucial for pancreatic endocrine lineage initiation. By monitoring both NEUROG3 gene expression and protein in single cells using a knockin dual reporter in 2D and 3D models of human pancreas development, we show an approximately 2-fold slower expression of human NEUROG3 than that of the mouse. We observe heterogeneous peak levels of NEUROG3 expression and reveal through long-term live imaging that both low and high NEUROG3 peak levels can trigger differentiation into hormone-expressing cells. Based on fluorescence intensity, we statistically integrate single-cell transcriptome with dynamic behaviors of live cells and propose a data-mapping methodology applicable to other contexts. Using this methodology, we identify a role for KLK12 in motility at the onset of NEUROG3 expression.
AU  - Beydag-Tasöz, B.S.*
AU  - D'Costa, J.V.*
AU  - Hersemann, L.*
AU  - Lee, B.H.*
AU  - Luppino, F.*
AU  - Kim, Y.H.*
AU  - Zechner, C.*
AU  - Grapin-Botton, A.
C1  - 67991
C2  - 54469
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 2292-2308.e6
TI  - Integrating single-cell imaging and RNA sequencing datasets links differentiation and morphogenetic dynamics of human pancreatic endocrine progenitors.
JO  - Dev. Cell
VL  - 58
IS  - 21
PB  - Cell Press
PY  - 2023
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Nuclear organization has emerged as a potential key regulator of genome function. During development, the deployment of transcriptional programs must be tightly coordinated with cell division and is often accompanied by major changes in the repertoire of expressed genes. These transcriptional and developmental events are paralleled by changes in the chromatin landscape. Numerous studies have revealed the dynamics of nuclear organization underlying them. In addition, advances in live-imaging-based methodologies enable the study of nuclear organization with high spatial and temporal resolution. In this Review, we summarize the current knowledge of the changes in nuclear architecture in the early embryogenesis of various model systems. Furthermore, to highlight the importance of integrating fixed-cell and live approaches, we discuss how different live-imaging techniques can be applied to examine nuclear processes and their contribution to our understanding of transcription and chromatin dynamics in early development. Finally, we provide future avenues for outstanding questions in this field.
AU  - Pecori, F.
AU  - Torres-Padilla, M.E.
C1  - 67656
C2  - 53963
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 435-449
TI  - Dynamics of nuclear architecture during early embryonic development and lessons from liveimaging.
JO  - Dev. Cell
VL  - 58
IS  - 6
PB  - Cell Press
PY  - 2023
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Non-alcoholic steatotic liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD has a major effect on the intrinsic proliferative properties of hepatocytes. Here, we investigated the mechanisms underlying the activation of DNA damage response during NAFLD. Proliferating mouse NAFLD hepatocytes harbor replication stress (RS) with an alteration of the replication fork's speed and activation of ATR pathway, which is sufficient to cause DNA breaks. Nucleotide pool imbalance occurring during NAFLD is the key driver of RS. Remarkably, DNA lesions drive cGAS/STING pathway activation, a major component of cells' intrinsic immune response. The translational significance of this study was reiterated by showing that lipid overload in proliferating HepaRG was sufficient to induce RS and nucleotide pool imbalance. Moreover, livers from NAFLD patients displayed nucleotide pathway deregulation and cGAS/STING gene alteration. Altogether, our findings shed light on the mechanisms by which damaged NAFLD hepatocytes might promote disease progression.
AU  - Donne, R.*
AU  - Saroul-Ainama, M.*
AU  - Cordier, P.*
AU  - Hammoutene, A.*
AU  - Kabore, C.*
AU  - Stadler, M.*
AU  - Nemazanyy, I.*
AU  - Galy-Fauroux, I.*
AU  - Herrag, M.*
AU  - Riedl, T.*
AU  - Chansel-Da Cruz, M.*
AU  - Caruso, S.*
AU  - Bonnafous, S.*
AU  - Öllinger, R.*
AU  - Rad, R.*
AU  - Unger, K.
AU  - Tran, A.*
AU  - Couty, J.P.*
AU  - Gual, P.*
AU  - Paradis, V.*
AU  - Celton-Morizur, S.*
AU  - Heikenwalder, M.*
AU  - Revy, P.*
AU  - Desdouets, C.*
C1  - 65680
C2  - 52886
SP  - 1728-1741.e6
TI  - Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD.
JO  - Dev. Cell
VL  - 57
IS  - 14
PY  - 2022
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Lipid droplets (LDs) are organelles of cellular lipid storage with fundamental roles in energy metabolism and cell membrane homeostasis. There has been an explosion of research into the biology of LDs, in part due to their relevance in diseases of lipid storage, such as atherosclerosis, obesity, type 2 diabetes, and hepatic steatosis. Consequently, there is an increasing need for a resource that combines datasets from systematic analyses of LD biology. Here, we integrate high-confidence, systematically generated human, mouse, and fly data from studies on LDs in the framework of an online platform named the “Lipid Droplet Knowledge Portal” (https://lipiddroplet.org/). This scalable and interactive portal includes comprehensive datasets, across a variety of cell types, for LD biology, including transcriptional profiles of induced lipid storage, organellar proteomics, genome-wide screen phenotypes, and ties to human genetics. This resource is a powerful platform that can be utilized to identify determinants of lipid storage.
AU  - Mejhert, N.*
AU  - Gabriel, K.R.*
AU  - Frendo-Cumbo, S.*
AU  - Krahmer, N.
AU  - Song, J.*
AU  - Kuruvilla, L.*
AU  - Chitraju, C.*
AU  - Boland, S.*
AU  - Jang, D.K.*
AU  - von Grotthuss, M.*
AU  - Costanzo, M.C.*
AU  - Rydén, M.*
AU  - Olzmann, J.A.*
AU  - Flannick, J.*
AU  - Burtt, N.P.*
AU  - Farese, R.V.*
C1  - 64229
C2  - 51798
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 387-397.e4
TI  - The Lipid Droplet Knowledge Portal: A resource for systematic analyses of lipid droplet biology.
JO  - Dev. Cell
VL  - 57
IS  - 3
PB  - Cell Press
PY  - 2022
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Understanding how complex cell-fate decisions emerge at the molecular level is a key challenge in developmental biology. Despite remarkable progress in decoding the contribution of the linear epigenome, how spatial genome architecture functionally informs changes in gene expression remains unclear. In this review, we discuss recent insights in elucidating the molecular landscape of genome folding, emphasizing the multilayered nature of the 3D genome, its importance for gene regulation, and its spatiotemporal dynamics. Finally, we discuss how these new concepts and emergent technologies will enable us to address some of the outstanding questions in development and disease.
AU  - Aboelnour, E.
AU  - Bonev, B.
C1  - 62030
C2  - 50577
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1562-1573
TI  - Decoding the organization, dynamics, and function of the 4D genome.
JO  - Dev. Cell
VL  - 56
IS  - 11
PB  - Cell Press
PY  - 2021
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness.
AU  - Benitez, S.*
AU  - Cordero, A.*
AU  - Santamaria, P.G.*
AU  - Redondo-Pedraza, J.*
AU  - Rocha, A.S.*
AU  - Collado-Solé, A.*
AU  - Jimenez, M.*
AU  - Sanz-Moreno, A.
AU  - Yoldi, G.*
AU  - Santos, J.C.*
AU  - De Benedictis, I.*
AU  - Gómez-Aleza, C.*
AU  - Da Silva-Álvarez, S.*
AU  - Troulé, K.*
AU  - Gómez-López, G.*
AU  - Alcazar, N.*
AU  - Palmero, I.*
AU  - Collado, M.*
AU  - Serrano, M.*
AU  - Gonzalez-Suarez, E.*
C1  - 62096
C2  - 50628
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1727-1741.e7
TI  - RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness.
JO  - Dev. Cell
VL  - 56
IS  - 12
PB  - Cell Press
PY  - 2021
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - How organ morphogenesis specifies cell fate and whether organ progenitors are predetermined or specified via niche signals are critical developmental biology questions. In this issue of Developmental Cell, Nyeng et al. (2019) modulate cell-cell adhesion in the pancreas and provide evidence that progenitors are plastic and instructed by niche signals.
AU  - Bakhti, M.
AU  - Bastidas-Ponce, A.
AU  - Lickert, H.
C1  - 55789
C2  - 46590
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1-3
TI  - Sorting out fate determination.
JO  - Dev. Cell
VL  - 49
IS  - 1
PB  - Cell Press
PY  - 2019
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The mechanism of how organ shape emerges and specifies cell fate is not understood. Pancreatic duct and endocrine lineages arise in a spatially distinct domain from the acinar lineage. Whether these lineages are pre-determined or settle once these niches have been established remains unknown. Here, we reconcile these two apparently opposing models, demonstrating that pancreatic progenitors re-localize to establish the niche that will determine their ultimate fate. We identify a p120ctn-regulated mechanism for coordination of organ architecture and cellular fate mediated by differential E-cadherin based cell sorting. Reduced p120ctn expression is necessary and sufficient to re-localize a subset of progenitors to the peripheral tip domain, where they acquire an acinar fate. The same mechanism is used re-iteratively during endocrine specification, where it balances the choice between the alpha and beta cell fates. In conclusion, organ patterning is regulated by p120ctn-mediated cellular positioning, which precedes and determines pancreatic progenitor fate.
AU  - Nyeng, P.*
AU  - Heilmann, S.*
AU  - Löf-Öhlin, Z.M.*
AU  - Pettersson, N.F.*
AU  - Hermann, F.M.*
AU  - Reynolds, A.B.*
AU  - Semb, H.
C1  - 55653
C2  - 46514
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 31-47.e9
TI  - P120ctn-mediated organ patterning precedes and determines pancreatic progenitor fate.
JO  - Dev. Cell
VL  - 49
IS  - 1
PB  - Cell Press
PY  - 2019
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Dormant cancer cells often survive treatment and increase the risk for tumor relapse, associated with dismal prognosis. Two recent papers describe mechanisms used by the bone marrow niche to regulate leukemia dormancy. The findings provide a molecular basis for niche-targeting therapies that may enable elimination of dormant tumor cells.
AU  - Senft, D.
AU  - Jeremias, I.
C1  - 55953
C2  - 46696
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 311-312
TI  - Tumor cell dormancy-triggered by the niche.
JO  - Dev. Cell
VL  - 49
IS  - 3
PB  - Cell Press
PY  - 2019
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - How cold-blooded animals acclimate to temperature and what determines the limits of their viable temperature range are not understood. Here, we show that Drosophila alter their dietary preference from yeast to plants when temperatures drop below 15 degrees C and that the different lipids present in plants improve survival at low temperatures. We show that Drosophila require dietary unsaturated fatty acids present in plants to adjust membrane fluidity and maintain motor coordination. Feeding on plants extends lifespan and survival for many months at temperatures consistent with overwintering in temperate climates. Thus, physiological alterations caused by a temperature-dependent dietary shift could help Drosophila survive seasonal temperature changes.
AU  - Brankatschk, M.*
AU  - Gutmann, T.
AU  - Knittelfelder, O.*
AU  - Palladini, A.
AU  - Prince, E.*
AU  - Grzybek, M.
AU  - Brankatschk, B.
AU  - Shevchenko, A.*
AU  - Coskun, Ü.
AU  - Eaton, S.*
C1  - 54402
C2  - 45546
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 781-793.e4
TI  - A temperature-dependent switch in feeding preference improves Drosophila development and survival in the cold.
JO  - Dev. Cell
VL  - 46
IS  - 6
PB  - Cell Press
PY  - 2018
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Lipid metabolism is highly compartmentalized between cellular organelles that dynamically adapt their compositions and interactions in response to metabolic challenges. Here, we investigate how diet-induced hepatic lipid accumulation, observed in non-alcoholic fatty liver disease (NAFLD), affects protein localization, organelle organization, and protein phosphorylation in vivo. We develop a mass spectrometric workflow for protein and phosphopeptide correlation profiling to monitor levels and cellular distributions of similar to 6,000 liver proteins and similar to 16,000 phosphopeptides during development of steatosis. Several organelle contact site proteins are targeted to lipid droplets (LDs) in steatotic liver, tethering organelles orchestrating lipid metabolism. Proteins of the secretory pathway dramatically redistribute, including the mis-localization of the COPI complex and sequestration of the Golgi apparatus at LDs. This correlates with reduced hepatic protein secretion. Our systematic in vivo analysis of subcellular rearrangements and organelle-specific phosphorylation reveals how nutrient overload leads to organellar reorganization and cellular dysfunction.
AU  - Krahmer, N.*
AU  - Najafi, B.
AU  - Schueder, F.*
AU  - Quagliarini, F.
AU  - Steger, M.*
AU  - Seitz, S.
AU  - Kasper, R.*
AU  - Salinas, F.*
AU  - Cox, J.*
AU  - Uhlenhaut, N.H.
AU  - Walther, T.C.*
AU  - Jungmann, R.*
AU  - Zeigerer, A.
AU  - Borner, G.H.H.*
AU  - Mann, M.*
C1  - 54573
C2  - 45681
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 205-221.e7
TI  - Organellar proteomics and phospho-proteomics reveal subcellular teorganization in diet-induced hepatic steatosis.
JO  - Dev. Cell
VL  - 47
IS  - 2
PB  - Cell Press
PY  - 2018
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The tripartite network of Prdm14, Blimp1, and AP2γ is essential for the important process of germ cell specification, but their precise molecular mechanisms of action remain lacking. Tu and colleagues (2016) report in Nature that the transcriptional co-repressor CBFA2T2 is an essential interactor protein regulating PRDM14 function, shedding light into the mechanisms directing germline formation and pluripotency.
AU  - Burton, A.
AU  - Torres-Padilla, M.E.
C1  - 49059
C2  - 41602
CY  - Cambridge
SP  - 3-5
TI  - A pluripotency platform for Prdm14.
JO  - Dev. Cell
VL  - 38
IS  - 1
PB  - Cell Press
PY  - 2016
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Proper morphogenesis of neuronal dendritic spines is essential for the formation of functional synaptic networks. However, it is not known how spines are initiated. Here, we identify the inverse-BAR (I-BAR) protein MIM/MTSS1 as a nucleator of dendritic spines. MIM accumulated to future spine initiation sites in a PIP2-dependent manner and deformed the plasma membrane outward into a proto-protrusion via its I-BAR domain. Unexpectedly, the initial protrusion formation did not involve actin polymerization. However, PIP2-dependent activation of Arp2/3-mediated actin assembly was required for protrusion elongation. Overexpression of MIM increased the density of dendritic protrusions and suppressed spine maturation. In contrast, MIM deficiency led to decreased density of dendritic protrusions and larger spine heads. Moreover, MIM-deficient mice displayed altered glutamatergic synaptic transmission and compatible behavioral defects. Collectively, our data identify an important morphogenetic pathway, which initiates spine protrusions by coupling phosphoinositide signaling, direct membrane bending, and actin assembly to ensure proper synaptogenesis.
AU  - Saarikangas, J.*
AU  - Kourdougli, N.*
AU  - Senju, Y.*
AU  - Chazal, G.*
AU  - Segerstrale, M.*
AU  - Minkeviciene, R.*
AU  - Kuurne, J.*
AU  - Mattila, P.K.*
AU  - Garrett, L.
AU  - Hölter, S.M.
AU  - Becker, L.
AU  - Rácz, I.*
AU  - Hans, W.
AU  - Klopstock, T.*
AU  - Wurst, W.
AU  - Zimmer, A.*
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Hrabě de Angelis, M.
AU  - von Ossowski, L.*
AU  - Taira, T.*
AU  - Lappalainen, P.*
AU  - Rivera, C.*
AU  - Hotulainen, P.*
C1  - 45124
C2  - 37224
CY  - Cambridge
SP  - 644-659
TI  - MIM-induced membrane bending promotes dendritic spine initiation.
JO  - Dev. Cell
VL  - 33
IS  - 6
PB  - Cell Press
PY  - 2015
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The regulation of neural stem cells is key to their use for repair. Reporting in this issue of Developmental Cell, Dirian et al. (2014) identify an adult neural stem cell population surprisingly distinct in Notch independence, lack of radial glia hallmarks, and late contribution to neurogenesis in a strikingly region-specific manner.
AU  - Ninkovic, J.
AU  - Götz, M.
C1  - 31846
C2  - 34814
CY  - Cambridge
SP  - 114-115
TI  - A time and place for understanding neural stem cell specification.
JO  - Dev. Cell
VL  - 30
IS  - 2
PB  - Cell Press
PY  - 2014
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - Speciation involves the reproductive isolation of natural populations due to the sterility or lethality of their hybrids. However, the molecular basis of hybrid lethality and the evolutionary driving forces that provoke it remain largely elusive. The hybrid male rescue (Hmr) and the lethal hybrid rescue (Lhr) genes serve as a model to study speciation in Drosophilids because their interaction causes lethality in male hybrid offspring. Here, we show that HMR and LHR form a centromeric complex necessary for proper chromosome segregation. We find that the Hmr expression level is substantially higher in Drosophila melanogaster, whereas Lhr expression levels are increased in Drosophila simulans. The resulting elevated amount of HMR/LHR complex in hybrids results in an extensive mislocalization of the complex, an interference with the regulation of transposable elements, and an impairment of cell proliferation. Our findings provide evidence for a major role of centromere divergence in the generation of biodiversity.
AU  - Thomae, A.W.*
AU  - Schade, G.O.*
AU  - Padeken, J.*
AU  - Borath, M.*
AU  - Vetter, I.*
AU  - Kremmer, E.
AU  - Heun, P.*
AU  - Imhof, A.*
C1  - 28441
C2  - 33381
SP  - 412-424
TI  - A pair of centromeric proteins mediates reproductive isolation in Drosophila species.
JO  - Dev. Cell
VL  - 27
IS  - 4
PB  - Cell Press
PY  - 2013
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The timing of commitment and cell-cycle exit within progenitor populations during neurogenesis is a fundamental decision that impacts both the number and identity of neurons produced during development. We show here that microRNA-9 plays a key role in this process through the direct inhibition of targets with antagonistic functions. Across the ventricular zone of the developing zebrafish hindbrain, miR-9 expression occurs at a range of commitment stages. Abrogating miR-9 function transiently delays cell-cycle exit, leading to the increased generation of late-born neuronal populations. Target protection analyses in vivo identify the progenitor-promoting genes her6 and zic5 and the cell-cycle exit-promoting gene elavl3/HuC as sequential targets of miR-9 as neurogenesis proceeds. We propose that miR-9 activity generates an ambivalent progenitor state poised to respond to both progenitor maintenance and commitment cues, which may be necessary to adjust neuronal production to local extrinsic signals during late embryogenesis.
AU  - Coolen, M.
AU  - Thieffry, D.*
AU  - Drivenes, O.*
AU  - Becker, T.S.*
AU  - Bally-Cuif, L.
C1  - 7530
C2  - 29786
SP  - 1052-1064
TI  - MiR-9 controls the timing of neurogenesis through the direct inhibition of antagonistic factors.
JO  - Dev. Cell
VL  - 22
IS  - 5
PB  - Cell Press
PY  - 2012
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked mental retardation gene product Dlg3 contributes to apical-basal polarity and epithelial junction formation in mouse organizer tissues, as well as to planar cell polarity in the inner ear. We purified complexes associated with Dlg3 in polarized epithelial cells, including proteins regulating directed trafficking and tight junction formation. Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs. We found that these interactions are required for Dlg3 monoubiquitination, apical membrane recruitment, and tight junction consolidation. Our findings reveal an unexpected evolutionary diversification of the vertebrate Dlg family in basolateral epithelium formation.
AU  - van Campenhout, C.A.
AU  - Eitelhuber, A.
AU  - Gloeckner, C.J.
AU  - Giallonardo, P.
AU  - Gegg, M.
AU  - Oller, H.
AU  - Grant, S.G.*
AU  - Krappmann, D.
AU  - Ueffing, M.
AU  - Lickert, H.
C1  - 5611
C2  - 28889
CY  - Cambridge, Mass.
SP  - 479-491
TI  - Dlg3 trafficking and apical tight junction formation is regulated by Nedd4 and Nedd4-2 E3 ubiquitin ligases.
JO  - Dev. Cell
VL  - 21
IS  - 3
PB  - Cell Press
PY  - 2011
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - A variety of developmental disorders have been associated with ciliary defects, yet the controls that govern cilia disassembly are largely unknown. Here we report a mouse embryonic node gene, which we named Pitchfork (Pifo). Pifo associates with ciliary targeting complexes and accumulates at the basal body during cilia disassembly. Haploinsufficiency causes a unique node cilia duplication phenotype, left-right asymmetry defects, and heart failure. This phenotype is likely relevant in humans, because we identified a heterozygous R80K PIFO mutation in a fetus with situs inversus and cystic liver and kidneys, and in patient with double-outflow right ventricle. We show that PIFO, but not R80K PIFO, is sufficient to activate Aurora A, a protooncogenic kinase that induces cilia retraction, and that Pifo/PIFO mutation causes cilia retraction, basal body liberation, and overreplication defects. Thus, the observation of a disassembly phenotype in vivo provides an entry point to understand and categorize ciliary disease.
AU  - Kinzel, D.
AU  - Boldt, K.
AU  - Davis, E.E.*
AU  - Burtscher, I.
AU  - Trümbach, D.
AU  - Diplas, B.*
AU  - Attie-Bitach, T.*
AU  - Wurst, W.
AU  - Katsanis, N.*
AU  - Ueffing, M.
AU  - Lickert, H.
C1  - 4868
C2  - 27416
SP  - 66-77
TI  - Pitchfork regulates primary cilia disassembly and left-right asymmetry.
JO  - Dev. Cell
VL  - 19
IS  - 1
PB  - Elsevier Inc.
PY  - 2010
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The habenular nuclei are a conserved relay center of telencephalic function, and they display bilateral asymmetry in many vertebrates. How this asymmetry is constructed in response to local lateralized cues remains poorly understood. A paper by Aizawa et al. (2007) in this issue of Developmental Cell highlights an unsuspected role for neuronal differentiation timing in the generation of structurally distinct left and right habenular nuclei. © 2007 Elsevier Inc. All rights reserved.
AU  - Bally-Cuif, L.
C1  - 3602
C2  - 24746
SP  - 1-2
TI  - Breaking symmetry on time.
JO  - Dev. Cell
VL  - 12
IS  - 1
PB  - Cell Press
PY  - 2007
SN  - 1534-5807
ER  - 

TY  - JOUR
AB  - The family of interferon-induced transmembrane protein (Ifitm/mil/fragilis) genes encodes cell surface proteins that may modulate cell adhesion and influence cell differentiation. Mouse Ifitm1 and -3, which are expressed in primordial germ cells (PGCs), are implicated to have roles in germ cell development, but the specific functions have been unclear. Our results show that Ifitm1 activity is required for PGC transit from the mesoderm into the endoderm, and that it appears to act via a repulsive mechanism, such that PGCs avoid Ifitm1-expressing tissues. In contrast, Ifitm3, which is expressed in migratory PGCs, is sufficient to confer autonomous PGC-like homing properties to somatic cells. These guidance activities are mediated by the N-terminal extracellular domain of the specific IFITM, which cannot be substituted by that of another family member. Complex homo- and/or heterotypic intercellular interactions among various IFITMs in PGCs and neighboring cells may underpin coordinated germ cell guidance in mice.
AU  - Tanaka, S.S.*
AU  - Yamaguchi, Y.L.*
AU  - Tsoi, B.*
AU  - Lickert, H.
AU  - Tam, P.P.L.*
C1  - 5054
C2  - 23059
SP  - 745-756
TI  - IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsing.
JO  - Dev. Cell
VL  - 9
IS  - 6
PY  - 2005
SN  - 1534-5807
ER  -