Cdx1 refines positional identity of the vertebrate hindbrain by directly repressing Mafb expression

Sturgeon, Kendra, Kaneko, Tomomi, Biemann, Melissa, Gauthier, Andree, Chawengsaksophak, Kallayanee and Cordes, Sabine P. (2011) Cdx1 refines positional identity of the vertebrate hindbrain by directly repressing Mafb expression. Development, 138 1: 65-74. doi:10.1242/dev.058727

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Author Sturgeon, Kendra
Kaneko, Tomomi
Biemann, Melissa
Gauthier, Andree
Chawengsaksophak, Kallayanee
Cordes, Sabine P.
Title Cdx1 refines positional identity of the vertebrate hindbrain by directly repressing Mafb expression
Journal name Development   Check publisher's open access policy
ISSN 0950-1991
Publication date 2011-01
Year available 2010
Sub-type Article (original research)
DOI 10.1242/dev.058727
Open Access Status File (Publisher version)
Volume 138
Issue 1
Start page 65
End page 74
Total pages 10
Place of publication United Kingdom
Publisher The Company of Biologists
Collection year 2012
Language eng
Abstract An interplay of transcription factors interprets signalling pathways to define anteroposterior positions along the vertebrate axis. In the hindbrain, these transcription factors prompt the position-appropriate appearance of seven to eight segmental structures, known as rhombomeres (r1-r8). The evolutionarily conserved Cdx caudal-type homeodomain transcription factors help specify the vertebrate trunk and tail but have not been shown to directly regulate hindbrain patterning genes. Mafb (Kreisler, Krml1, valentino), a basic domain leucine zipper transcription factor, is required for development of r5 and r6 and is the first gene to show restricted expression within these two segments. The homeodomain protein vHnf1 (Hnf1b) directly activates Mafb expression. vHnf1 and Mafb share an anterior expression limit at the r4/r5 boundary but vHnf1 expression extends beyond the posterior limit of Mafb and, therefore, cannot establish the posterior Mafb expression boundary. Upon identifying regulatory sequences responsible for posterior Mafb repression, we have used in situ hybridization, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses to determine that Cdx1 directly inhibits early Mafb expression in the neural tube posterior of the r6/r7 boundary, which is the anteriormost boundary of Cdx1 expression in the hindbrain. Cdx1 dependent repression of Mafb is transient. After the 10-somite stage, another mechanism acts to restrict Mafb expression in its normal r5 and r6 domain, even in the absence of Cdx1. Our findings identify Mafb as one of the earliest direct targets of Cdx1 and show that Cdx1 plays a direct role in early hindbrain patterning. Thus, just as Cdx2 and Cdx4 govern the trunk-to-tail transition, Cdx1 may regulate the hindbrain-to-spinal cord transition.
Keyword Axial patterning
Caudal related proteins (Cdx)
Developmental gene regulation
Hindbrain patterning
Mafb (Kreisler)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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Created: Sat, 30 Jul 2011, 20:47:25 EST by Dr Kallayanee Chawengsaksophak on behalf of School of Biomedical Sciences