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  • 1.
    Kropp, Marlene
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Wilson, Sara I.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    The expression profile of the tumor suppressor gene Lzts1 suggests a role in neuronal development2012In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 241, no 5, p. 984-994Article in journal (Refereed)
    Abstract [en]

    Background: Neuronal circuit assembly comprises a number of developmental processes that ultimately underlie function. Identifying the molecular events that dictate these processes can give key insights into how neuronal circuit formation is coordinated. To begin to identify such molecular mechanisms, we have analysed the expression of a candidate gene of entirely unknown function within the nervous system. Here we reveal the spatial and temporal distribution of Lzts1 in mouse and chick embryonic spinal cord and propose potential biological functions. Results: Lzts1 mRNA is transiently expressed at the border of the ventricular and mantle zones in subsets of sensory and motor spinal neurons. The protein is localized to the cell body, axon, and trailing process of motor, commissural, and dorsal root neurons during development. Conclusions: Taken together, the spatial and temporal distribution of Lzts1 is consistent with a potential function(s) in cell cycle regulation, axon growth or guidance, and/or migration of neurons. Developmental Dynamics 241:984994, 2012. (c) 2012 Wiley Periodicals, Inc.

  • 2.
    Laumonnerie, Christophe
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Da Silva, Ronan V.
    Kania, Artur
    Wilson, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Netrin 1 and Dcc signalling are required for confinement of central axons within the central nervous system2014In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 141, no 3, p. 594-603Article in journal (Refereed)
    Abstract [en]

    The establishment of anatomically stereotyped axonal projections is fundamental to neuronal function. While most neurons project their axons within the central nervous system (CNS), only axons of centrally born motoneurons and peripherally born sensory neurons link the CNS and peripheral nervous system (PNS) together by navigating through specialized CNS/PNS transition zones. Such selective restriction is of importance because inappropriate CNS axonal exit could lead to loss of correct connectivity and also to gain of erroneous functions. However, to date, surprisingly little is known about the molecular-genetic mechanisms that regulate how central axons are confined within the CNS during development. Here, we show that netrin 1/Dcc/Unc5 chemotropism contributes to axonal confinement within the CNS. In both Ntn1 and Dcc mutant mouse embryos, some spinal interneuronal axons exit the CNS by traversing the CNS/PNS transition zones normally reserved for motor and sensory axons. We provide evidence that netrin 1 signalling preserves CNS/PNS axonal integrity in three ways: (1) netrin 1/Dcc ventral attraction diverts axons away from potential exit points; (2) a Dcc/Unc5c-dependent netrin 1 chemoinhibitory barrier in the dorsolateral spinal cord prevents interneurons from being close to the dorsal CNS/PNS transition zone; and (3) a netrin 1/Dcc-dependent, Unc5c-independent mechanism that actively prevents exit from the CNS. Together, these findings provide insights into the molecular mechanisms that maintain CNS/PNS integrity and, to the best of our knowledge, present the first evidence that chemotropic signalling regulates interneuronal CNS axonal confinement in vertebrates.

  • 3.
    Laumonnerie, Christophe
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Tong, Yong Guang
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Alstermark, Helena
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Wilson, Sara I.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Commissural axonal corridors instruct neuronal migration in the mouse spinal cord2015In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, article id 7028Article in journal (Refereed)
    Abstract [en]

    Unravelling how neurons are guided during vertebrate embryonic development has wide implications for understanding the assembly of the nervous system. During embryogenesis, migration of neuronal cell bodies and axons occurs simultaneously, but to what degree they influence each other's development remains obscure. We show here that within the mouse embryonic spinal cord, commissural axons bisect, delimit or preconfigure ventral interneuron cell body position. Furthermore, genetic disruption of commissural axons results in abnormal ventral interneuron cell body positioning. These data suggest that commissural axonal fascicles instruct cell body position by acting either as border landmarks (axon-restricted migration), which to our knowledge has not been previously addressed, or acting as cellular guides. This study in the developing spinal cord highlights an important function for the interaction of cell bodies and axons, and provides a conceptual proof of principle that is likely to have overarching implications for the development of neuronal architecture.

  • 4.
    Wilson, Sara I
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Target practice: Zic2 hits the bullseye!2010In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 29, no 18, p. 3037-3038Article in journal (Refereed)
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