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Neural Development

Burcu Erdogan, Garrett M Cammarata, Eric J Lee, Benjamin C Pratt, Andrew F Francl, Erin L Rutherford, Laura Anne Lowery
BACKGROUND: Formation of precise neuronal connections requires proper axon guidance. Microtubules (MTs) of the growth cone provide a critical driving force during navigation of the growing ends of axons. Pioneer MTs and their plus-end tracking proteins (+TIPs) are thought to play integrative roles during this navigation. TACC3 is a + TIP that we have previously implicated in regulating MT dynamics within axons. However, the role of TACC3 in axon guidance has not been previously explored...
February 15, 2017: Neural Development
Eerdunfu, Naoki Ihara, Bao Ligao, Yuji Ikegaya, Haruki Takeuchi
BACKGROUND: The mammalian primary olfactory system has a spatially-ordered projection in which olfactory sensory neurons (OSNs) located in the dorsomedial (DM) and ventrolateral (VL) region of the olfactory epithelium (OE) send their axons to the dorsal and ventral region of the olfactory bulb (OB), respectively. We previously found that OSN axonal projections occur sequentially, from the DM to the VL region of the OE. The differential timing of axonal projections is important for olfactory map formation because early-arriving OSN axons secrete guidance cues at the OB to help navigate late-arriving OSN axons...
February 13, 2017: Neural Development
Keiko Hirono, Minoree Kohwi, Matt Q Clark, Ellie S Heckscher, Chris Q Doe
BACKGROUND: Drosophila and mammalian neural progenitors typically generate a diverse family of neurons in a stereotyped order. Neuronal diversity can be generated by the sequential expression of temporal transcription factors. In Drosophila, neural progenitors (neuroblasts) sequentially express the temporal transcription factors Hunchback (Hb), Kruppel, Pdm, and Castor. Hb is necessary and sufficient to specify early-born neuronal identity in multiple lineages, and is maintained in the post-mitotic neurons produced during each neuroblast expression window...
January 31, 2017: Neural Development
Michelle Ware, Houda Hamdi-Rozé, Julien Le Friec, Véronique David, Valérie Dupé
BACKGROUND: Neurons arise in very specific regions of the neural tube, controlled by components of the Notch signalling pathway, proneural genes, and other bHLH transcription factors. How these specific neuronal areas in the brain are generated during development is just beginning to be elucidated. Notably, the critical role of proneural genes during differentiation of the neuronal populations that give rise to the early axon scaffold in the developing brain is not understood. The regulation of their downstream effectors remains poorly defined...
December 7, 2016: Neural Development
Peter J Bosch, Leah C Fuller, Carolyn M Sleeth, Joshua A Weiner
BACKGROUND: The proper spatial and temporal regulation of dorsal telencephalic progenitor behavior is a prerequisite for the formation of the highly-organized, six-layered cerebral cortex. Premature differentiation of cells, disruption of cell cycle timing, excessive apoptosis, and/or incorrect neuronal migration signals can have devastating effects, resulting in a number of neurodevelopmental disorders involving microcephaly and/or lissencephaly. Though genes encoding many key players in cortical development have been identified, our understanding remains incomplete...
November 21, 2016: Neural Development
Candace M Marsters, Jessica M Rosin, Hayley F Thornton, Shaghayegh Aslanpour, Natasha Klenin, Grey Wilkinson, Carol Schuurmans, Quentin J Pittman, Deborah M Kurrasch
BACKGROUND: Although the vast majority of cells in our brains are glia, we are only beginning to understand programs governing their development, especially within the embryonic hypothalamus. In mice, gliogenesis is a protracted process that begins during embryonic stages and continues into the early postnatal period, with glial progenitors first producing oligodendrocyte precursor cells, which then differentiate into pro-oligodendrocytes, pro-myelinating oligodendrocytes, and finally, mature myelinating oligodendrocytes...
November 18, 2016: Neural Development
Harald J Junge, Andrea R Yung, Lisa V Goodrich, Zhe Chen
BACKGROUND: Newborn neurons often migrate before undergoing final differentiation, extending neurites, and forming synaptic connections. Therefore, neuronal migration is crucial for establishing neural circuitry during development. In the developing spinal cord, neuroprogenitors first undergo radial migration within the ventricular zone. Differentiated neurons continue to migrate tangentially before reaching the final positions. The molecular pathways that regulate these migration processes remain largely unknown...
October 26, 2016: Neural Development
Brielle Bjorke, Farnaz Shoja-Taheri, Minkyung Kim, G Eric Robinson, Tatiana Fontelonga, Kyung-Tai Kim, Mi-Ryoung Song, Grant S Mastick
BACKGROUND: Oculomotor neurons develop initially like typical motor neurons, projecting axons out of the ventral midbrain to their ipsilateral targets, the extraocular muscles. However, in all vertebrates, after the oculomotor nerve (nIII) has reached the extraocular muscle primordia, the cell bodies that innervate the superior rectus migrate to join the contralateral nucleus. This motor neuron migration represents a unique strategy to form a contralateral motor projection. Whether migration is guided by diffusible cues remains unknown...
October 22, 2016: Neural Development
Emilie Legué, Jackie L Gottshall, Edouard Jaumouillé, Alberto Roselló-Díez, Wei Shi, Luis Humberto Barraza, Senna Washington, Rachel L Grant, Alexandra L Joyner
BACKGROUND: The mouse cerebellum (Cb) has a remarkably complex foliated three-dimensional (3D) structure, but a stereotypical cytoarchitecture and local circuitry. Little is known of the cellular behaviors and genes that function during development to determine the foliation pattern. In the anteroposterior axis the mammalian cerebellum is divided by lobules with distinct sizes, and the foliation pattern differs along the mediolateral axis defining a medial vermis and two lateral hemispheres...
September 8, 2016: Neural Development
Torrey L S Truszkowski, Eric J James, Mashfiq Hasan, Tyler J Wishard, Zhenyu Liu, Kara G Pratt, Hollis T Cline, Carlos D Aizenman
BACKGROUND: Fragile X Syndrome is the leading monogenetic cause of autism and most common form of intellectual disability. Previous studies have implicated changes in dendritic spine architecture as the primary result of loss of Fragile X Mental Retardation Protein (FMRP), but recent work has shown that neural proliferation is decreased and cell death is increased with either loss of FMRP or overexpression of FMRP. The purpose of this study was to investigate the effects of loss of FMRP on behavior and cellular activity...
August 8, 2016: Neural Development
Christine Pérez, Darrell Sawmiller, Jun Tan
Autism Spectrum Disorders (ASD) are the second most common developmental cause of disability in the United States. ASDs are accompanied with substantial economic and emotional cost. The brains of ASD patients have marked structural abnormalities, in the form of increased dendritic spines and decreased long distance connections. These structural differences may be due to deficiencies in Heparin Sulfate (HS), a proteoglycan involved in a variety of neurodevelopmental processes. Of particular interest is its role in the Slit/Robo pathway...
April 18, 2016: Neural Development
Paola Lepanto, Camila Davison, Gabriela Casanova, Jose L Badano, Flavio R Zolessi
BACKGROUND: Retinal ganglion cell (RGC) differentiation in vivo is a highly stereotyped process, likely resulting from the interaction of cell type-specific transcription factors and tissue-derived signaling factors. The primary cilium, as a signaling hub in the cell, may have a role during this process but its presence and localization during RGC generation, and its contribution to the process of cell differentiation, have not been previously assessed in vivo. METHODS: In this work we analyzed the distribution of primary cilia in vivo using laser scanning confocal microscopy, as well as their main ultrastructural features by transmission electron microscopy, in the early stages of retinal histogenesis in the zebrafish, around the time of RGC generation and initial differentiation...
April 6, 2016: Neural Development
Giuliana Caronia-Brown, Angela Anderegg, Rajeshwar Awatramani
BACKGROUND: Brain size and patterning are dependent on dosage-sensitive morphogen signaling pathways - yet how these pathways are calibrated remains enigmatic. Recent studies point to a new role for microRNAs in tempering the spatio-temporal range of morphogen functions during development. Here, we investigated the role of miR-135a, derived from the mir-135a-2 locus, in embryonic forebrain development. METHOD: 1. We characterized the expression of miR-135a, and its host gene Rmst, by in situ hybridization (ish)...
April 5, 2016: Neural Development
Brock Grill, Rodney K Murphey, Melissa A Borgen
During development, a coordinated and integrated series of events must be accomplished in order to generate functional neural circuits. Axons must navigate toward target cells, build synaptic connections, and terminate outgrowth. The PHR proteins (consisting of mammalian Phr1/MYCBP2, Drosophila Highwire and C. elegans RPM-1) function in each of these events in development. Here, we review PHR function across species, as well as the myriad of signaling pathways PHR proteins regulate. These findings collectively suggest that the PHR proteins are intracellular signaling hubs, a concept we explore in depth...
March 23, 2016: Neural Development
Ivan Gladwyn-Ng, Lieven Huang, Linh Ngo, Shan Shan Li, Zhengdong Qu, Hannah Kate Vanyai, Hayley Daniella Cullen, John Michael Davis, Julian Ik-Tsen Heng
BACKGROUND: The development of neural circuits within the embryonic cerebral cortex relies on the timely production of neurons, their positioning within the embryonic cerebral cortex as well as their terminal differentiation and dendritic spine connectivity. The RhoA GTPases Rnd2 and Rnd3 are important for neurogenesis and cell migration within the embryonic cortex (Nat Commun 4:1635, 2013), and we recently identified the BTB/POZ domain-containing Adaptor for Cul3-mediated RhoA Degradation family member Bacurd2 (also known as Tnfaip1) as an interacting partner to Rnd2 for the migration of embryonic mouse cortical neurons (Neural Dev 10:9, 2015)...
March 11, 2016: Neural Development
José L Juárez-Morales, Claus J Schulte, Sofia A Pezoa, Grace K Vallejo, William C Hilinski, Samantha J England, Sarah de Jager, Katharine E Lewis
BACKGROUND: For neurons to function correctly in neuronal circuitry they must utilize appropriate neurotransmitters. However, even though neurotransmitter specificity is one of the most important and defining properties of a neuron we still do not fully understand how neurotransmitter fates are specified during development. Most neuronal properties are determined by the transcription factors that neurons express as they start to differentiate. While we know a few transcription factors that specify the neurotransmitter fates of particular neurons, there are still many spinal neurons for which the transcription factors specifying this critical phenotype are unknown...
February 19, 2016: Neural Development
Gerard W O'Keeffe, Humberto Gutierrez, Laura Howard, Christopher W Laurie, Catarina Osorio, Núria Gavaldà, Sean L Wyatt, Alun M Davies
BACKGROUND: Nerve growth factor (NGF) is the prototypical target-derived neurotrophic factor required for sympathetic neuron survival and for the growth and ramification of sympathetic axons within most but not all sympathetic targets. This implies the operation of additional target-derived factors for regulating terminal sympathetic axon growth and branching. RESULTS: Here report that growth differentiation factor 5 (GDF5), a widely expressed member of the transforming growth factor beta (TGFβ) superfamily required for limb development, promoted axon growth from mouse superior cervical ganglion (SCG) neurons independently of NGF and enhanced axon growth in combination with NGF...
February 15, 2016: Neural Development
Cedric Patthey, Harry Clifford, Wilfried Haerty, Chris P Ponting, Sebastian M Shimeld, Jo Begbie
BACKGROUND: The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process. RESULTS: Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq...
January 27, 2016: Neural Development
Olga Y Ponomareva, Kevin W Eliceiri, Mary C Halloran
BACKGROUND: Charcot-Marie-Tooth2b (CMT2b) is an axonal form of a human neurodegenerative disease that preferentially affects sensory neurons. CMT2b is dominantly inherited and is characterized by unusually early onset, presenting in the second or third decade of life. Five missense mutations in the gene encoding Rab7 GTPase have been identified as causative in human CMT2b disease. Although several studies have modeled CMT2b disease in cultured neurons and in Drosophila, the mechanisms by which defective Rab7 leads to disease remain poorly understood...
January 20, 2016: Neural Development
Pradeepa Jayachandran, Valerie N Olmo, Stephanie P Sanchez, Rebecca J McFarland, Eudorah Vital, Jonathan M Werner, Elim Hong, Neus Sanchez-Alberola, Aleksey Molodstov, Rachel M Brewster
BACKGROUND: Shaping of the neural tube, the precursor of the brain and spinal cord, involves narrowing and elongation of the neural tissue, concomitantly with other morphogenetic changes that contribue to this process. In zebrafish, medial displacement of neural cells (neural convergence or NC), which drives the infolding and narrowing of the neural ectoderm, is mediated by polarized migration and cell elongation towards the dorsal midline. Failure to undergo proper NC results in severe neural tube defects, yet the molecular underpinnings of this process remain poorly understood...
January 18, 2016: Neural Development
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