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Tytuł:
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Pax6 modulates intra-retinal axon guidance and fasciculation of retinal ganglion cells during retinogenesis.
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Autorzy:
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Lalitha S; Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala, 695 014, India.; Research Centre, The University of Kerala, Thiruvananthapuram, Kerala, 695 014, India.
Basu B; Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala, 695 014, India.; Regional Centre for Biotechnology, Faridabad, Haryana, 121 001, India.
Surya S; Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala, 695 014, India.; Research Centre, The University of Kerala, Thiruvananthapuram, Kerala, 695 014, India.
Meera V; Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala, 695 014, India.; Research Centre, The University of Kerala, Thiruvananthapuram, Kerala, 695 014, India.
Riya PA; Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala, 695 014, India.; Research Centre, The University of Kerala, Thiruvananthapuram, Kerala, 695 014, India.
Parvathy S; Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala, 695 014, India.; Research Centre, The University of Kerala, Thiruvananthapuram, Kerala, 695 014, India.
Das AV; Cancer Biology Programs-12, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695 014, India.
Sivakumar KC; Bioinformatics Facility, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695 014, India.
Nelson-Sathi S; Interdisciplinary Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695 014, India.
James J; Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Thiruvananthapuram, Kerala, 695 014, India. .; Research Centre, The University of Kerala, Thiruvananthapuram, Kerala, 695 014, India. .; Regional Centre for Biotechnology, Faridabad, Haryana, 121 001, India. .
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Źródło:
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Scientific reports [Sci Rep] 2020 Sep 30; Vol. 10 (1), pp. 16075. Date of Electronic Publication: 2020 Sep 30.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: London : Nature Publishing Group, copyright 2011-
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MeSH Terms:
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Axon Fasciculation/*physiology
Axon Guidance/*physiology
PAX6 Transcription Factor/*physiology
Retinal Ganglion Cells/*physiology
Animals ; Axon Fasciculation/genetics ; Axon Guidance/genetics ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Extracellular Matrix/metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurogenesis/genetics ; Neurogenesis/physiology ; PAX6 Transcription Factor/deficiency ; PAX6 Transcription Factor/genetics ; Pregnancy ; RNA-Seq ; Receptor, EphB1/genetics ; Receptor, EphB1/physiology ; Retina/embryology ; Retina/growth & development ; Retina/physiology ; Retinal Ganglion Cells/cytology ; Semaphorins/genetics ; Semaphorins/physiology
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References:
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Substance Nomenclature:
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0 (PAX6 Transcription Factor)
0 (Pax6 protein, mouse)
0 (Semaphorins)
EC 2.7.10.1 (Receptor, EphB1)
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Entry Date(s):
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Date Created: 20201001 Date Completed: 20210104 Latest Revision: 20210930
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Update Code:
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20240105
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PubMed Central ID:
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PMC7527980
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DOI:
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10.1038/s41598-020-72828-4
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PMID:
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32999322
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Intra-retinal axon guidance involves a coordinated expression of transcription factors, axon guidance genes, and secretory molecules within the retina. Pax6, the master regulator gene, has a spatio-temporal expression typically restricted till neurogenesis and fate-specification. However, our observation of persistent expression of Pax6 in mature RGCs led us to hypothesize that Pax6 could play a major role in axon guidance after fate specification. Here, we found significant alteration in intra-retinal axon guidance and fasciculation upon knocking out of Pax6 in E15.5 retina. Through unbiased transcriptome profiling between Pax6 fl/fl and Pax6 -/- retinas, we revealed the mechanistic insight of its role in axon guidance. Our results showed a significant increase in the expression of extracellular matrix molecules and decreased expression of retinal fate specification and neuron projection guidance molecules. Additionally, we found that EphB1 and Sema5B are directly regulated by Pax6 owing to the guidance defects and improper fasciculation of axons. We conclude that Pax6 expression post fate specification of RGCs is necessary for regulating the expression of axon guidance genes and most importantly for maintaining a conducive ECM through which the nascent axons get guided and fasciculate to reach the optic disc.