Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning

Elaine Y.M Wong; Xing An Wang; Siu Shan Mak; Jearn Jang Sae-Pang; Kam Wing Ling; Bernd Fritzsch; Mai Har Sham

doi:10.1016/j.ydbio.2011.02.003

Back

Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning

Journal article

Open access

Peer reviewed

Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning

Elaine Y.M Wong, Xing An Wang, Siu Shan Mak, Jearn Jang Sae-Pang, Kam Wing Ling, Bernd Fritzsch and Mai Har Sham

Developmental biology, Vol.352(2), pp.382-392

04/15/2011

DOI: 10.1016/j.ydbio.2011.02.003

PMID: 21320481

Files and links (1)

url

https://doi.org/10.1016/j.ydbio.2011.02.003View

Published (Version of record) Open Access

Abstract

The spatial regulation of combinatorial expression of Hox genes is critical for determining hindbrain rhombomere (r) identities. To address the cross-regulatory relationship between Hox genes in hindbrain neuronal specification, we have generated a gain-of-function transgenic mouse mutant Hoxb3Tg using the Hoxb2 r4-specific enhancer element. Interestingly, in r4 of the Hoxb3Tg mutant where Hoxb3 was ectopically expressed, the expression of Hoxb1 was specifically abolished. The hindbrain neuronal defects of the Hoxb3Tg mutant mice were similar to those of Hoxb1−/− mutants. Therefore, we hypothesized that Hoxb3 could directly suppress Hoxb1 expression. We first identified a novel Hoxb3 binding site S3 on the Hoxb1 locus and confirmed protein binding to this site by EMSA, and by in vivo ChIP analysis using P19 cells and hindbrain tissues from the Hoxb3Tg mutant. We further showed that Hoxb3 could suppress Hoxb1 transcriptional activity by chick in ovo luciferase reporter assay. Moreover, in E10.5 wildtype caudal hindbrain, where Hoxb1 is not expressed, we showed by in vivo ChIP that Hoxb3 was consistently bound to the S3 site on the Hoxb1 gene. This study reveals a novel negative regulatory mechanism by which Hoxb3 as a posterior gene serves to restrict Hoxb1 expression in r4 by direct transcriptional repression to maintain the rhombomere identity. ► We generated a gain-of-function Hoxb3Tg transgenic mutant which expressed Hoxb3 in hindbrain r4. ► Hoxb3Tg embryos lost Hoxb1 expression in the mutant r4 and phenocopy Hoxb1 null mutants. ► By molecular analyses we showed that Hoxb3 can suppress Hoxb1 expression directly. ► We demonstrated that Hoxb3 can restrict Hoxb1 expression to r4 by a negative regulatory mechanism.

Posterior prevalence

Rhombomere 4

Hoxb3

Neuronal identity

Hoxb1

Facial branchiomotor neurons

Neurogenesis

Hindbrain patterning

Hox gene regulation

Details

Title: Subtitle: Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning
Creators: Elaine Y.M Wong - Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Xing An Wang - Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Siu Shan Mak - Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Jearn Jang Sae-Pang - Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Kam Wing Ling - Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Bernd Fritzsch - Department of Biology, The University of Iowa, USA
Mai Har Sham - Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Resource Type: Journal article
Publication Details: Developmental biology, Vol.352(2), pp.382-392
DOI: 10.1016/j.ydbio.2011.02.003
PMID: 21320481
NLM abbreviation: Dev Biol
ISSN: 0012-1606
eISSN: 1095-564X
Publisher: Elsevier Inc
Grant note: name: Hong Kong Research Grants Council, award: HKU7294/98M, HKU2/01C, HKU4/05C, HKU775209M
Language: English
Date published: 04/15/2011
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070785902771

Metrics

24 Record Views

17 Times Cited - Web of Science