Functional dissection of the Pax6 paired domain: Roles in neural tube patterning and peripheral nervous system development.
Dev. Biol. 413, 86-103 (2016)
During development of the CNS, stem and progenitor cell proliferation, cell fate designation, and patterning decisions are tightly regulated by interdependent networks of key transcriptional regulators. In a genetic approach we analyzed divergent functionality of the PAI and RED sub-domains of the Pax6 Paired domain (PD) during progenitor zone formation, motor and interneuron development, and peripheral connectivity at distinct levels within the neural tube: within the hindbrain, mutation of the PAI sub-domain severely affected patterning of the p3 and pMN domains and establishment of the corresponding motor neurons. Exit point designation of hypoglossal axons was disturbed in embryos harboring either mutations in the PD sub-domains or containing a functional Pax6 Null allele. At brachial spinal levels, we propose a selective involvement of the PAI sub-domain during patterning of ventral p2 and pMN domains, critically disturbing generation of specific motor neuron subtypes and increasing V2 interneuron numbers. Our findings present a novel aspect of how Pax6 not only utilizes its modular structure to perform distinct functions via its paired and homeodomain. Individual sub-domains can exert distinct functions, generating a new level of complexity for transcriptional regulation by one single transcription factor not only in dorso-ventral, but also rostro-caudal neural tube patterning.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Bi-partite Paired Domain ; Lmc ; Mmc ; Neural Tube Patterning ; Pax6 ; Somatic Motor Neurons ; V2 Interneurons; Progenitor-cell Identity; Motor-neuron; Spinal-cord; Signaling Pathway; Homeobox Genes; Axon Guidance; Specification; Eye; Differentiation; Homeodomain
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2016
Prepublished im Jahr
2015
HGF-Berichtsjahr
2015
ISSN (print) / ISBN
0012-1606
e-ISSN
0012-1606
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 413,
Heft: 1,
Seiten: 86-103
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
San Diego
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30204 - Cell Programming and Repair
Forschungsfeld(er)
Genetics and Epidemiology
Stem Cell and Neuroscience
PSP-Element(e)
G-500592-001
G-500800-001
Förderungen
Copyright
Erfassungsdatum
2015-07-20