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Takashi Namba, Samir Vaid, Wieland Huttner
Primate neocortex development and evolution: Conserved versus evolved folding.
J Comp Neurol, 527(10) 1621-1632 (2019)
PubMed Source   

The neocortex, the seat of higher cognitive functions, exhibits a key feature across mammalian species-a highly variable degree of folding. Within the neocortex, two distinct subtypes of cortical areas can be distinguished, the isocortex and the proisocortex. Here, we have compared specific spatiotemporal aspects of folding between the proisocortex and the isocortex in 13 primates, including human, chimpanzee, and various Old World and New World monkeys. We find that folding at the boundaries of the dorsal isocortex and the proisocortex, which gives rise to the cingulate sulcus (CiS) and the lateral fissure (LF), is conserved across the primates studied and is therefore referred to as conserved folding. In contrast, the degree of folding within the dorsal isocortex exhibits huge variation across these primates, indicating that this folding, which gives rise to gyri and sulci, is subject to major changes during primate evolution. We therefore refer to the folding within the dorsal isocortex as evolved folding. Comparison of fetal neocortex development in long-tailed macaque and human reveals that the onset of conserved folding precedes the onset of evolved folding. Moreover, the analysis of infant human neocortex exhibiting lissencephaly, a developmental malformation thought to be mainly due to abnormal neuronal migration, shows that the evolved folding is perturbed more than the conserved folding. Taken together, our study presents a two-step model of folding that pertains to primate neocortex development and evolution. Specifically, our data imply that the conserved folding and the evolved folding constitute two distinct, sequential events.
@article{Namba7305,
author={Takashi Namba, Samir Vaid, Wieland Huttner},
title={Primate neocortex development and evolution: Conserved versus evolved folding.},
journal ={The Journal of comparative neurology},
volume={527},
issue ={10},
pages={1621--1632},
year=2019
}

Titus Franzmann, Simon Alberti
Prion-like low-complexity sequences: Key regulators of protein solubility and phase behavior.
J Biol Chem, 294(18) 7128-7136 (2019)
PubMed Source   

Many proteins, such as RNA-binding proteins, have complex folding landscapes. How cells maintain the solubility and folding state of such proteins, particularly under stress conditions, is largely unknown. Here, we argue that prion-like low-complexity regions (LCRs) are key regulators of protein solubility and folding. We discuss emerging evidence that prion-like LCRs are not, as commonly thought, autonomous aggregation modules that adopt amyloid-like conformations, but protein-specific sequences with chaperone-like functions. On the basis of recent findings, we propose that prion-like LCRs have evolved to regulate protein phase behavior and to protect proteins against proteotoxic damage.
@article{Franzmann7169,
author={Titus Franzmann, Simon Alberti},
title={Prion-like low-complexity sequences: Key regulators of protein solubility and phase behavior.},
journal ={The Journal of biological chemistry},
volume={294},
issue ={18},
pages={7128--7136},
year=2019
}

Anneke Wilharm, Inga Sandrock, Marie Marotel, Abdi Demera, Ronald Naumann, Thierry Walzer, Immo Prinz
Styk1 is specifically expressed in NK1.1+ lymphocytes including NK, γδ T, and iNKT cells in mice, but is dispensable for their ontogeny and function.
Eur J Immunol, 49(5) 686-693 (2019)
PubMed Source   

Innate T cells, NK cells, and innate-like lymphocytes (ILCs) share transcriptional signatures that translate into overlapping developmental and functional programs. A prominent example for genes that are highly expressed in NK cells but not in ILCs is serine-threonine-tyrosine kinase 1 (Styk1 encoded by Styk1). We found Styk1 to be specifically expressed in lymphocytes positive for Killer cell lectin-like receptor subfamily B, member 1, also known as CD161 or NK1.1, i.e. in NK cell, αβ iNKT, and γδ NKT cell lineages. To investigate the role of Styk1 in the development and function of NK1.1+ innate T-cell subsets, we generated and analyzed a novel Styk1null mutant mouse line. Furthermore, we validated Styk1 expression in γδ NKT cells and in thymic, but not in peripheral invariant αβ iNKT cells through ex vivo analysis of a concomitantly generated transgenic Styk1 reporter mouse line. Despite the very specific expression of Styk1 in NK cells, γδ NKT cells, and thymic αβ iNKT, its absence did not alter homeostasis and function of these lineages. Thus, Styk1 expression is specific for NK cells and selected NK-like innate T-cell subsets, but dispensable for their development and function.
@article{Wilharm7338,
author={Anneke Wilharm, Inga Sandrock, Marie Marotel, Abdi Demera, Ronald Naumann, Thierry Walzer, Immo Prinz},
title={Styk1 is specifically expressed in NK1.1+ lymphocytes including NK, γδ T, and iNKT cells in mice, but is dispensable for their ontogeny and function.},
journal ={European journal of immunology},
volume={49},
issue ={5},
pages={686--693},
year=2019
}

Milos Kostic, Judith Paridaen, Katherine S. Long, Nereo Kalebic, Barbara Langen, Nannette Grübling, Pauline Wimberger, Hiroshi Kawasaki, Takashi Namba, Wieland Huttner
YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex.
Cell Rep, 27(4) 1103-1118 (2019)
PubMed Source   

Neocortex expansion during mammalian evolution has been linked to an increase in proliferation of basal progenitors in the subventricular zone. Here, we explored a potential role of YAP, the major downstream effector of the Hippo pathway, in proliferation of basal progenitors. YAP expression and activity are high in ferret and human basal progenitors, which exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. Conditional expression of a constitutively active YAP in mouse basal progenitors resulted in increased proliferation of basal progenitor and promoted production of upper-layer neurons. Pharmacological and genetic interference with YAP function in ferret and human developing neocortex resulted in decreased abundance of cycling basal progenitors. Together, our data indicate that YAP is necessary and sufficient to promote the proliferation of basal progenitors and suggest that increases in YAP levels and presumably activity contributed to the evolutionary expansion of the neocortex.
@article{Kostic7390,
author={Milos Kostic, Judith Paridaen, Katherine S. Long, Nereo Kalebic, Barbara Langen, Nannette Grübling, Pauline Wimberger, Hiroshi Kawasaki, Takashi Namba, Wieland Huttner},
title={YAP Activity Is Necessary and Sufficient for Basal Progenitor Abundance and Proliferation in the Developing Neocortex.},
journal ={Cell reports},
volume={27},
issue ={4},
pages={1103--1118},
year=2019
}

Satu Kujawski, Mahendra Sonawane, Elisabeth Knust
penner/lgl2 is required for the integrity of the photoreceptor layer in the zebrafish retina.
Biol Open, 8(4) Art. No. bio041830 (2019)
PubMed Source   

The vertebrate retina is a complex tissue built from multiple neuronal cell types, which develop from a pseudostratified neuroepithelium. These cells are arranged into a highly organized and stereotypic pattern formed by nuclear and plexiform layers. The process of lamination as well as the maturation and differentiation of photoreceptor cells rely on the establishment and maintenance of apico-basal cell polarity and formation of adhesive junctions. Defects in any of these processes can result in impaired vision and are causally related to a variety of human diseases leading to blindness. While the importance of apical polarity regulators in retinal stratification and disease is well established, little is known about the function of basal regulators in retinal development. Here, we analyzed the role of Lgl2, a basolateral polarity factor, in the zebrafish retina. Lgl2 is upregulated in photoreceptor cells and in the retinal pigment epithelium by 72 h post fertilization. In both cell types, Lgl2 is localized basolaterally. Loss of zygotic Lgl2 does not interfere with retinal lamination or photoreceptor cell polarity or maturation. However, knockdown of both maternal and zygotic Lgl2 leads to impaired cell adhesion. As a consequence, severe layering defects occur in the distal retina, manifested by a breakdown of the outer plexiform layer and the outer limiting membrane. These results define zebrafish Lgl2 as an important regulator of retinal lamination, which, given the high degree of evolutionary conservation, may be preserved in other vertebrates, including human.
@article{Kujawski7391,
author={Satu Kujawski, Mahendra Sonawane, Elisabeth Knust},
title={penner/lgl2 is required for the integrity of the photoreceptor layer in the zebrafish retina.},
journal ={Biology open},
volume={8},
issue ={4},
pages={1--1},
year=2019
}

Martina Ugrinic, Andrew deMello, T-Y Dora Tang
Microfluidic Tools for Bottom-Up Synthetic Cellularity
Chem, Art. No. https://doi.org/10.1016/j.chempr.2019.03.012 (2019)
 

@article{Ugrinic7389,
author={Martina Ugrinic, Andrew deMello, T-Y Dora Tang},
title={Microfluidic Tools for Bottom-Up Synthetic Cellularity},
journal ={Chem},
volume={},
pages={1--1},
year=2019
}

Landi Sun, Yuan Gao, Jianfeng He, Lihong Cui, Jana Meissner, Jean-Marc Verbavatz, Bo Li, Xiqiao Feng, Xin Liang
Ultrastructural organization of NompC in the mechanoreceptive organelle of Drosophila campaniform mechanoreceptors.
Proc Natl Acad Sci U.S.A., 116(15) 7343-7352 (2019)
PubMed Source   

Mechanoreceptive organelles (MOs) are specialized subcellular entities in mechanoreceptors that transform extracellular mechanical stimuli into intracellular signals. Their ultrastructures are key to understanding the molecular nature and mechanics of mechanotransduction. Campaniform sensilla detect cuticular strain caused by muscular activities or external stimuli in Drosophila Each campaniform sensillum has an MO located at the distal tip of its dendrite. Here we analyzed the molecular architecture of the MOs in fly campaniform mechanoreceptors using electron microscopic tomography. We focused on the ultrastructural organization of NompC (a force-sensitive channel) that is linked to the array of microtubules in these MOs via membrane-microtubule connectors (MMCs). We found that NompC channels are arranged in a regular pattern, with their number increasing from the distal to the proximal end of the MO. Double-length MMCs in nompC 29+29ARs confirm the ankyrin-repeat domain of NompC (NompC-AR) as a structural component of MMCs. The unexpected finding of regularly spaced NompC-independent linkers in nompC3 suggests that MMCs may contain non-NompC components. Localized laser ablation experiments on mechanoreceptor arrays in halteres suggest that MMCs bear tension, providing a possible mechanism for why the MMCs are longer when NompC-AR is duplicated or absent in mutants. Finally, mechanical modeling shows that upon cuticular deformation, sensillar architecture imposes a rotational activating force, with the proximal end of the MO, where more NOMPC channels are located, being subject to larger forces than the distal end. Our analysis reveals an ultrastructural pattern of NompC that is structurally and mechanically optimized for the sensory functions of campaniform mechanoreceptors.
@article{Sun7375,
author={Landi Sun, Yuan Gao, Jianfeng He, Lihong Cui, Jana Meissner, Jean-Marc Verbavatz, Bo Li, Xiqiao Feng, Xin Liang},
title={Ultrastructural organization of NompC in the mechanoreceptive organelle of Drosophila campaniform mechanoreceptors.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={116},
issue ={15},
pages={7343--7352},
year=2019
}

Nereo Kalebic, Carlotta Gilardi, Barbara Stepien, Michaela Wilsch-Bräuninger, Katherine S. Long, Takashi Namba, Marta Florio, Barbara Langen, Benoit Lombardot, Anna Shevchenko, Manfred W Kilimann, Hiroshi Kawasaki, Pauline Wimberger, Wieland Huttner
Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology.
Cell Stem Cell, 24(4) 535-550 (2019)
PubMed Source   

The evolutionary expansion of the mammalian neocortex (Ncx) is thought to be linked to increased proliferative capacity of basal progenitors (BPs) and their neurogenic capacity. Here, by quantifying BP morphology in the developing Ncx of mouse, ferret, and human, we show that increased BP proliferative capacity is linked to an increase in BP process number. We identify human membrane-bound PALMDELPHIN (PALMD-Caax) as an underlying factor, and we show that it drives BP process growth and proliferation when expressed in developing mouse and ferret Ncx. Conversely, CRISPR/Cas9-mediated disruption of PALMD or its binding partner ADDUCIN-γ in fetal human Ncx reduces BP process numbers and proliferation. We further show that PALMD-induced processes enable BPs to receive pro-proliferative integrin-dependent signals. These findings provide a link between BP morphology and proliferation, suggesting that changes in BP morphology may have contributed to the evolutionary expansion of the Ncx.
@article{Kalebic7370,
author={Nereo Kalebic, Carlotta Gilardi, Barbara Stepien, Michaela Wilsch-Bräuninger, Katherine S. Long, Takashi Namba, Marta Florio, Barbara Langen, Benoit Lombardot, Anna Shevchenko, Manfred W Kilimann, Hiroshi Kawasaki, Pauline Wimberger, Wieland Huttner},
title={Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology.},
journal ={Cell stem cell},
volume={24},
issue ={4},
pages={535--550},
year=2019
}

Barbara Stepien, Wieland Huttner
Transport, Metabolism, and Function of Thyroid Hormones in the Developing Mammalian Brain.
Front Endocrinol (Lausanne), 10 Art. No. 209 (2019)
PubMed Source   

Ever since the discovery of thyroid hormone deficiency as the primary cause of cretinism in the second half of the 19th century, the crucial role of thyroid hormone (TH) signaling in embryonic brain development has been established. However, the biological understanding of TH function in brain formation is far from complete, despite advances in treating thyroid function deficiency disorders. The pleiotropic nature of TH action makes it difficult to identify and study discrete roles of TH in various aspect of embryogenesis, including neurogenesis and brain maturation. These challenges notwithstanding, enormous progress has been achieved in understanding TH production and its regulation, their conversions and routes of entry into the developing mammalian brain. The endocrine environment has to adjust when an embryo ceases to rely solely on maternal source of hormones as its own thyroid gland develops and starts to produce endogenous TH. A number of mechanisms are in place to secure the proper delivery and action of TH with placenta, blood-brain interface, and choroid plexus as barriers of entry that need to selectively transport and modify these hormones thus controlling their active levels. Additionally, target cells also possess mechanisms to import, modify and bind TH to further fine-tune their action. A complex picture of a tightly regulated network of transport proteins, modifying enzymes, and receptors has emerged from the past studies. TH have been implicated in multiple processes related to brain formation in mammals-neuronal progenitor proliferation, neuronal migration, functional maturation, and survival-with their exact roles changing over developmental time. Given the plethora of effects thyroid hormones exert on various cell types at different developmental periods, the precise spatiotemporal regulation of their action is of crucial importance. In this review we summarize the current knowledge about TH delivery, conversions, and function in the developing mammalian brain. We also discuss their potential role in vertebrate brain evolution and offer future directions for research aimed at elucidating TH signaling in nervous system development.
@article{Stepien7387,
author={Barbara Stepien, Wieland Huttner},
title={Transport, Metabolism, and Function of Thyroid Hormones in the Developing Mammalian Brain.},
journal ={Frontiers in endocrinology},
volume={10},
pages={null--null},
year=2019
}

Johannes Klaus, Sabina Kanton, Christina Kyrousi, Ane Cristina Ayo-Martin, Rossella Di Giaimo, Stephan Riesenberg, Adam C O'Neill, J Gray Camp, Chiara Tocco, Malgorzata Santel, Ejona Rusha, Micha Drukker, Mariana Schroeder, Magdalena Götz, Stephen P Robertson, Barbara Treutlein, Silvia Cappello
Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia.
Nat Med, 25(4) 561-568 (2019)
PubMed Source   

Malformations of the human cortex represent a major cause of disability1. Mouse models with mutations in known causal genes only partially recapitulate the phenotypes and are therefore not unlimitedly suited for understanding the molecular and cellular mechanisms responsible for these conditions2. Here we study periventricular heterotopia (PH) by analyzing cerebral organoids derived from induced pluripotent stem cells (iPSCs) of patients with mutations in the cadherin receptor-ligand pair DCHS1 and FAT4 or from isogenic knockout (KO) lines1,3. Our results show that human cerebral organoids reproduce the cortical heterotopia associated with PH. Mutations in DCHS1 and FAT4 or knockdown of their expression causes changes in the morphology of neural progenitor cells and result in defective neuronal migration dynamics only in a subset of neurons. Single-cell RNA-sequencing (scRNA-seq) data reveal a subpopulation of mutant neurons with dysregulated genes involved in axon guidance, neuronal migration and patterning. We suggest that defective neural progenitor cell (NPC) morphology and an altered navigation system in a subset of neurons underlie this form of PH.
@article{Klaus7369,
author={Johannes Klaus, Sabina Kanton, Christina Kyrousi, Ane Cristina Ayo-Martin, Rossella Di Giaimo, Stephan Riesenberg, Adam C O'Neill, J Gray Camp, Chiara Tocco, Malgorzata Santel, Ejona Rusha, Micha Drukker, Mariana Schroeder, Magdalena Götz, Stephen P Robertson, Barbara Treutlein, Silvia Cappello},
title={Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia.},
journal ={Nature medicine},
volume={25},
issue ={4},
pages={561--568},
year=2019
}