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Roy, A.* ; Francius, C.* ; Rousso, D.L.* ; Seuntjens, E.* ; Debruyn, J.* ; Luxenhofer, G. ; Huber, A.B. ; Huylebroeck, D.* ; Novitch, B.G.* ; Clotman, F.*

Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification.

Development 139, 3109-3119 (2012)
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During development, spinal motoneurons (MNs) diversify into a variety of subtypes that are specifically dedicated to the motor control of particular sets of skeletal muscles or visceral organs. MN diversification depends on the coordinated action of several transcriptional regulators including the LIM-HD factor Isl1, which is crucial for MN survival and fate determination. However, how these regulators cooperate to establish each MN subtype remains poorly understood. Here, using phenotypic analyses of single or compound mutant mouse embryos combined with gain-of-function experiments in chick embryonic spinal cord, we demonstrate that the transcriptional activators of the Onecut family critically regulate MN subtype diversification during spinal cord development. We provide evidence that Onecut factors directly stimulate Isl1 expression in specific MN subtypes and are therefore required to maintain Isl1 production at the time of MN diversification. In the absence of Onecut factors, we observed major alterations in MN fate decision characterized by the conversion of somatic to visceral MNs at the thoracic levels of the spinal cord and of medial to lateral MNs in the motor columns that innervate the limbs. Furthermore, we identify Sip1 (Zeb2) as a novel developmental regulator of visceral MN differentiation. Taken together, these data elucidate a comprehensive model wherein Onecut factors control multiple aspects of MN subtype diversification. They also shed light on the late roles of Isl1 in MN fate decision.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Onecut Factors ; Isl1 ; Sip1 ; Neuronal Diversification ; Spinal Cord ; Cns Development; Hepatocyte Nuclear Factor-6; Motor-Neuron Identity; Smad-Interacting Protein-1; Lim Homeobox Genes; Subtype Identity; Homeodomain Proteins; Expression Pattern; Mammalian Member; Nervous-System; Mouse Embryo
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Quellenangaben Band: 139, Heft: 17, Seiten: 3109-3119 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Begutachtungsstatus Peer reviewed