Format

Send to

Choose Destination
Dev Biol. 2016 Jan 15;409(2):530-42. doi: 10.1016/j.ydbio.2015.11.006. Epub 2015 Nov 26.

Analyses of fugu hoxa2 genes provide evidence for subfunctionalization of neural crest cell and rhombomere cis-regulatory modules during vertebrate evolution.

Author information

1
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
2
Stowers Institute for Medical Research, Kansas City, MO 64110, USA. Electronic address: tuempel@fli-leibniz.de.
3
Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, KS 66160, USA.
4
Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Anatomy and Cell Biology, Kansas University Medical Center, Kansas City, KS 66160, USA. Electronic address: rek@stowers.org.

Abstract

Hoxa2 gene is a primary player in regulation of craniofacial programs of head development in vertebrates. Here we investigate the evolution of a Hoxa2 neural crest enhancer identified originally in mouse by comparing and contrasting the fugu hoxa2a and hoxa2b genes with their orthologous teleost and mammalian sequences. Using sequence analyses in combination with transgenic regulatory assays in zebrafish and mouse embryos we demonstrate subfunctionalization of regulatory activity for expression in hindbrain segments and neural crest cells between these two fugu co-orthologs. hoxa2a regulatory sequences have retained the ability to mediate expression in neural crest cells while those of hoxa2b include cis-elements that direct expression in rhombomeres. Functional dissection of the neural crest regulatory potential of the fugu hoxa2a and hoxa2b genes identify the previously unknown cis-element NC5, which is implicated in generating the differential activity of the enhancers from these genes. The NC5 region plays a similar role in the ability of this enhancer to mediate reporter expression in mice, suggesting it is a conserved component involved in control of neural crest expression of Hoxa2 in vertebrate craniofacial development.

KEYWORDS:

Enhancers; Evolution of cis-elements; Gene regulation; Hindbrain; Hox genes; Neural crest

PMID:
26632170
DOI:
10.1016/j.ydbio.2015.11.006
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center