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isthmic organizer

Chelsea U Kidwell, Chen-Ying Su, Masahiko Hibi, Cecilia B Moens
A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum...
June 1, 2018: Developmental Biology
Junwon Lee, Sang-Hwi Choi, Dongjin R Lee, Dae-Sung Kim, Dong-Wook Kim
The objective of this study was to induce the production of isthmic organizer (IsO)-like cells capable of secreting fibroblast growth factor (FGF) 8 and WNT1 from human embryonic stem cells (ESCs). The precise modulation of canonical Wnt signaling was achieved in the presence of the small molecule CHIR99021 (0.6 μM) during the neural induction of human ESCs, resulting in the differentiation of these cells into IsO-like cells having a midbrain-hindbrain border (MHB) fate in a manner that recapitulated their developmental course in vivo ...
February 28, 2018: Molecules and Cells
Keiko Muguruma
Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies...
February 2018: Cerebellum
Joanna Yeung, Daniel Goldowitz
Wntless (Wls) is implicated in the Wnt signaling pathway by regulating the secretion of Wnt molecules. During brain development, Wls is expressed in the isthmic organizer (ISO) and rhombic lip (RL). Wls regulates Wnt1 secretion at the ISO which is required to induce midbrain-hindbrain structures. However, Wls function in the RL is not known. Here, we employed Nestin-cre to delete Wls specifically in the RL during mid-gestation. The loss-of-Wls leads to an abnormal RL during development and cerebellar vermis hypoplasia at birth...
June 23, 2017: Neuroscience
Keiko Muguruma
Pluripotent stem cells (PSCs) possess self-organizing abilities in 3D culture. This property has been demonstrated in recent studies, including the generation of various neuroectodermal and endodermal tissues. For example, PSCs are able to differentiate into specific type of neural tissues, such as the neocortex and the optic cup, in response to local positional information brought about by signals during embryogenesis. In contrast, the generation of cerebellar tissue from PSCs requires a secondary induction by a signaling center, called the isthmic organizer, which first appears in the cell aggregate in 3D culture...
2017: Methods in Molecular Biology
Alexander Dee, Kairong Li, Xin Heng, Qiuxia Guo, James Y H Li
The embryonic tectum displays an anteroposterior gradient in development and produces the superior colliculus and inferior colliculus. Studies suggest that partition of the tectum is controlled by different strengths and durations of FGF signals originated from the so-called isthmic organizer at the mid/hindbrain junction; however, the underlying mechanism is unclear. We show that deleting Ptpn11, which links FGF with the ERK pathway, prevents inferior colliculus formation by depleting a previously uncharacterized stem cell zone...
October 15, 2016: Development
Julián Yáñez, Yara Souto, Laura Piñeiro, Mónica Folgueira, Ramón Anadón
The central connections of the gustatory/general visceral system of the adult zebrafish (Danio rerio) were examined by means of carbocyanine dye tracing. Main primary gustatory centers (facial and vagal lobes) received sensory projections from the facial and vagal nerves, respectively. The vagal nerve also projects to the commissural nucleus of Cajal, a general visceral sensory center. These primary centers mainly project on a prominent secondary gustatory and general visceral nucleus (SGN/V) located in the isthmic region...
February 1, 2017: Journal of Comparative Neurology
Camilla Bosone, Abraham Andreu, Diego Echevarria
Gap junctions (GJs) are integral membrane proteins that enable the direct cytoplasmic exchange of ions and low molecular weight metabolites between adjacent cells. They are formed by the apposition of two connexons belonging to adjacent cells. Each connexon is formed by six proteins, named connexins (Cxs). Current evidence suggests that gap junctions play an important part in ensuring normal embryo development. Mutations in connexin genes have been linked to a variety of human diseases, although the precise role and the cell biological mechanisms of their action remain almost unknown...
June 2016: Development, Growth & Differentiation
Soojin Kim, Yangu Zhao, Ja-Myong Lee, Woon Ryoung Kim, Marat Gorivodsky, Heiner Westphal, Dongho Geum
LIM domain-binding protein 1 (Ldb1) is a nuclear cofactor that interacts with LIM homeodomain proteins to form multiprotein complexes that are important for transcription regulation. Ldb1 has been shown to play essential roles in various processes during mouse embryogenesis. To determine the role of Ldb1 in mid- and hindbrain development, we have generated a conditional mutant with a specific deletion of the Ldb1 in the Engrailed-1-expressing region of the developing mid- and hindbrain. Our study showed that the deletion impaired the expression of signaling molecules, such as fibroblast growth factor 8 (FGF8) and Wnt1, in the isthmic organizer and the expression of Shh in the ventral midbrain...
July 1, 2016: Stem Cells and Development
Melina Rapacioli, Verónica Palma, Vladimir Flores
The central nervous system areas displaying the highest structural and functional complexity correspond to the so called cortices, i.e., concentric alternating neuronal and fibrous layers. Corticogenesis, i.e., the development of the cortical organization, depends on the temporal-spatial organization of several developmental events: (a) the duration of the proliferative phase of the neuroepithelium, (b) the relative duration of symmetric (expansive) versus asymmetric (neuronogenic) sub phases, (c) the spatial organization of each kind of cell division, (e) the time of determination and cell cycle exit and (f) the time of onset of the post-mitotic neuronal migration and (g) the time of onset of the neuronal structural and functional differentiation...
2016: Frontiers in Cellular Neuroscience
Willemieke M Kouwenhoven, Jesse V Veenvliet, Johannes A van Hooft, L P van der Heide, Marten P Smidt
The isthmic organizer (IsO) is a signaling center that specifies the correct and distinct embryonic development of the dopaminergic midbrain and serotonergic hindbrain. The IsO is a linear boundary between the two brain regions, emerging at around embryonic day 7-8 of murine embryonic development, that shapes its surroundings through the expression of instructive signals such as Wnt and growth factors. Homeobox transcription factor engrailed 1 (En1) is present in midbrain and rostral hindbrain (i.e. rhombomere 1, R1)...
2016: Biology Open
Sol Pose-Méndez, Eva Candal, Sylvie Mazan, Isabel Rodríguez-Moldes
The cerebellum is present in all extant gnathostomes or jawed vertebrates, of which cartilaginous fishes represent the most ancient radiation. Since the isthmic organizer induces the formation of the cerebellum, comparative genoarchitectonic analysis on the meso-isthmo-cerebellar region of cartilaginous fishes with respect to that of jawless vertebrates could reveal why the isthmic organizer acquires the ability to induce the formation of the cerebellum in gnathostomes. In the present work we analyzed the expression pattern of a variety of genes related to the cerebellar formation and patterning (ScOtx2, ScGbx2, ScFgf8, ScLmx1b, ScIrx1, ScIrx3, ScEn2, ScPax6 and ScLhx9) by in situ hybridization, and the distribution of Pax6 protein in the developing hindbrain of the shark Scyliorhinus canicula...
April 2016: Brain Structure & Function
Y Yoshimoto, Y Yamamoto, Y Kobayashi, I Woclawek-Potocka, E Sinderewicz, K Okuda
The oviduct is an essential organ for successful pregnancy in mammals. The transport of gametes and early embryos is mainly induced by contraction and relaxation of smooth muscle. The contraction and relaxation of bovine oviductal smooth muscle are induced by prostaglandin (PG) F2α and PGE2, respectively. Lysophosphatidic acid (LPA), a type of phospholipid, is involved in various physiological actions such as promoting inflammation and cellular proliferation in various organs. LPA acts through at least 6 G protein-coupled receptors...
December 2014: Reproduction, Fertility, and Development
Pablo Cruz-Martinez, Almudena Martinez-Ferre, Jesus Jaramillo-Merchán, Alicia Estirado, Salvador Martinez, Jonathan Jones
Fibroblast growth factor 8 (FGF8) is a key molecular signal that is necessary for early embryonic development of the central nervous system, quickly disappearing past this point. It is known to be one of the primary morphogenetic signals required for cell fate and survival processes in structures such as the cerebellum, telencephalic and isthmic organizers, while its absence causes severe abnormalities in the nervous system and the embryo usually dies in early stages of development. In this work, we have observed a new possible therapeutic role for this factor in demyelinating disorders, such as leukodystrophy or multiple sclerosis...
2014: PloS One
Shiori Uezono, Yusuke Yamada, Takeshi Kato, Hideki Abe, Naoyuki Yamamoto
The primary general visceral nucleus of teleosts is called the commissural nucleus of Cajal (NCC). The NCC of goldfish has been divided into the medial (NCCm) and lateral (NCCl) subnuclei that receive inputs from subdiaphragmatic gastrointestinal tract and the posterior pharynx, respectively. Fiber connections of the NCC were examined by tract-tracing methods in the goldfish Carassius auratus. Tracer injections into the NCC suggested that the NCC projects directly not only to the secondary visceral sensory region in the rhombencephalic isthmus and other brain stem centers, but also to the forebrain, similar to the situations in mammals, birds, and the Nile tilapia...
February 1, 2015: Journal of Comparative Neurology
Kathleen J Millen, Ekaterina Y Steshina, Igor Y Iskusnykh, Victor V Chizhikov
Model organism studies have demonstrated that cell fate specification decisions play an important role in normal brain development. Their role in human neurodevelopmental disorders, however, is poorly understood, with very few examples described. The cerebellum is an excellent system to study mechanisms of cell fate specification. Although signals from the isthmic organizer are known to specify cerebellar territory along the anterior-posterior axis of the neural tube, the mechanisms establishing the cerebellar anlage along the dorsal-ventral axis are unknown...
April 29, 2014: Proceedings of the National Academy of Sciences of the United States of America
Matthew T Whitehead, Asim F Choudhri, John Grimm, Marvin D Nelson
BACKGROUND: Rhombencephalosynapsis is a rare genetic aberration characterized by variable vermian hypoplasia/aplasia in conjunction with united cerebellar hemispheres. Genetic defects in the isthmic organizer at the mesencephalic-metencephalic junction are presumably responsible for the associated aqueductal stenosis. OBJECTIVE: We performed a retrospective review of 20 children with rhombencephalosynapsis to evaluate for and emphasize the association of aqueductal stenosis and hydrocephalus...
July 2014: Pediatric Radiology
Luca G Di Giovannantonio, Michela Di Salvio, Daniela Omodei, Nilima Prakash, Wolfgang Wurst, Alessandra Pierani, Dario Acampora, Antonio Simeone
During embryonic development, the rostral neuroectoderm is regionalized into broad areas that are subsequently subdivided into progenitor compartments with specialized identity and fate. These events are controlled by signals emitted by organizing centers and interpreted by target progenitors, which activate superimposing waves of intrinsic factors restricting their identity and fate. The transcription factor Otx2 plays a crucial role in mesencephalic development by positioning the midbrain-hindbrain boundary (MHB) and its organizing activity...
January 2014: Development
Stefan Weigel, Harald Luksch
The chicken optic tectum (TeO) and its mammalian counterpart, the superior colliculus, are important sensory integration centers. Multimodal information is represented in a topographic map, which plays a role in spatial attention and orientation movements. The TeO is organised in 15 layers with clear input and output regions, and further interconnected with the isthmic nuclei (NI), which modulate the response in a winner-takes-all fashion. While many studies have analysed tectal cell types and their modulation from the isthmic system physiologically, little is known about local network activity and its modulation in the tectum...
March 2014: European Journal of Neuroscience
Linda Z Holland, João E Carvalho, Hector Escriva, Vincent Laudet, Michael Schubert, Sebastian M Shimeld, Jr-Kai Yu
The question of whether the ancestral bilaterian had a central nervous system (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable evidence supports the theory that a CNS evolved just once. However, an alternative view proposes that the chordate CNS evolved from the ectodermal nerve net of a hemichordate-like ancestral deuterostome, implying independent evolution of the CNS in chordates and protostomes. To specify morphological divisions along the anterior/posterior axis, this ancestor used gene networks homologous to those patterning three organizing centers in the vertebrate brain: the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent evolution of the vertebrate brain involved elaboration of these ancestral signaling centers; however, all or part of these signaling centers were lost from the CNS of invertebrate chordates...
2013: EvoDevo
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