The Enhancer of split transcription factor Her8a is a novel dimerisation partner for Her3 that controls anterior hindbrain neurogenesis in zebrafish. - Archive ouverte HAL Access content directly
Journal Articles BMC Developmental Biology Year : 2011

The Enhancer of split transcription factor Her8a is a novel dimerisation partner for Her3 that controls anterior hindbrain neurogenesis in zebrafish.

(1, 2, 3) , (1, 4) , (5, 6) , (1, 7) , (1, 8) , (1, 9) , (5, 6) , (1, 4)
1
2
3
4
5
6
7
8
9

Abstract

BACKGROUND: Neurogenesis control and the prevention of premature differentiation in the vertebrate embryo are crucial processes, allowing the formation of late-born cell types and ensuring the correct shape and cytoarchitecture of the brain. Members of the Hairy/Enhancer of Split (Hairy/E(spl)) family of bHLH-Orange transcription factors, such as zebrafish Her3, 5, 9 and 11, are implicated in the local inhibition of neurogenesis to maintain progenitor pools within the early neural plate. To better understand how these factors exert their inhibitory function, we aimed to isolate some of their functional interactors. RESULTS: We used a yeast two-hybrid screen with Her5 as bait and recovered a novel zebrafish Hairy/E(spl) factor--Her8a. Using phylogenetic and synteny analyses, we demonstrate that her8a evolved from an ancient duplicate of Hes6 that was recently lost in the mammalian lineage. We show that her8a is expressed across the mid- and anterior hindbrain from the start of segmentation. Through knockdown and misexpression experiments, we demonstrate that Her8a is a negative regulator of neurogenesis and plays an essential role in generating progenitor pools within rhombomeres 2 and 4--a role resembling that of Her3. Her8a co-purifies with Her3, suggesting that Her8a-Her3 heterodimers may be relevant in this domain of the neural plate, where both proteins are co-expressed. Finally, we demonstrate that her8a expression is independent of Notch signaling at the early neural plate stage but that SoxB factors play a role in its expression, linking patterning information to neurogenesis control. Overall, the regulation and function of Her8a differ strikingly from those of its closest relative in other vertebrates--the Hes6-like proteins. CONCLUSIONS: Our results characterize the phylogeny, expression and functional interactions involving a new Her factor, Her8a, and highlight the complex interplay of E(spl) proteins that generates the neurogenesis pattern of the zebrafish early neural plate.
Fichier principal
Vignette du fichier
1471-213X-11-27.pdf (4.7 Mo) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S1.DOC (139.5 Ko) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S2.DOC (44.5 Ko) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S3.PDF (3.05 Mo) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S4.JPEG (1.17 Mo) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S5.JPEG (1.19 Mo) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S6.JPEG (1.76 Mo) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S7.JPEG (995.28 Ko) Télécharger le fichier
Vignette du fichier
1471-213X-11-27-S8.DOC (31.5 Ko) Télécharger le fichier
Vignette du fichier
1471-213X-11-27.xml (127.22 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other

Dates and versions

inserm-00622822 , version 1 (12-09-2011)

Identifiers

Cite

Katharine Webb, Marion Coolen, Christian Gloeckner, Christian Stigloher, Brigitte Bahn, et al.. The Enhancer of split transcription factor Her8a is a novel dimerisation partner for Her3 that controls anterior hindbrain neurogenesis in zebrafish.. BMC Developmental Biology, 2011, 11 (1), pp.27. ⟨10.1186/1471-213X-11-27⟩. ⟨inserm-00622822⟩
399 View
366 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More