PuSH - Publikationsserver des Helmholtz Zentrums München

Geling, A. ; Itoh, M.* ; Tallafuß, A. ; Chapouton, P. ; Tannhäuser, B. ; Kuwada, J.Y.* ; Chitnis, A.B.* ; Bally-Cuif, L.

bHLH transcription factor Her5 links patterning to regional inhibition of neurogenesis at the midbrain-hindbrain boundary.

Development 130, 1591-1604 (2003)
Verlagsversion DOI
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The midbrain-hindbrain (MH) domain of the vertebrate embryonic neural plate displays a stereotypical profile of neuronal differentiation, organized around a neuron-free zone ('intervening zone', IZ) at the midbrain-hindbrain boundary (MHB). The mechanisms establishing this early pattern of neurogenesis are unknown. We demonstrate that the MHB is globally refractory to neurogenesis, and that forced neurogenesis in this area interferes with the continued expression of genes defining MHB identity. We further show that expression of the zebrafish bHLH Hairy/E(spl)-related factor Her5 prefigures and then precisely delineates the IZ throughout embryonic development. Using morpholino knock-down and conditional gain-of-function assays, we demonstrate that Her5 is essential to prevent neuronal differentiation and promote cell proliferation in a medial compartment of the IZ. We identify one probable target of this activity, the zebrafish Cdk inhibitor p27Xic1. Finally, although the her5 expression domain is determined by anteroposterior patterning cues, we show Her5 does not retroactively influence MH patterning. Together, our results highlight the existence of a mechanism that actively inhibits neurogenesis at the MHB, a process that shapes MH neurogenesis into a pattern of separate neuronal clusters and might ultimately be necessary to maintain MHB integrity. Her5 appears as a partially redundant component of this inhibitory process that helps translate early axial patterning information into a distinct spatiotemporal pattern of neurogenesis and cell proliferation within the MH domain.
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Bhlh ; Cyclin-dependent Kinase Inhibitor ; E(spl) ; Hairy ; Her5 ; Mhb ; Midbrain-hindbrain Boundary ; Neurogenesis ; P27 ; Proliferation ; Zebrafish
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Quellenangaben Band: 130, Heft: 8, Seiten: 1591-1604 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Begutachtungsstatus Peer reviewed