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XB-ART-52838
Dev Biol January 15, 2017; 421 (2): 171-182.

Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development.

Neilson KM , Abbruzzesse G , Kenyon K , Bartolo V , Krohn P , Alfandari D , Moody SA .


Abstract
Mutations in SIX1 and in its co-factor, EYA1, underlie Branchiootorenal Spectrum disorder (BOS), which is characterized by variable branchial arch, otic and kidney malformations. However, mutations in these two genes are identified in only half of patients. We screened for other potential co-factors, and herein characterize one of them, Pa2G4 (aka Ebp1/Plfap). In human embryonic kidney cells, Pa2G4 binds to Six1 and interferes with the Six1-Eya1 complex. In Xenopus embryos, knock-down of Pa2G4 leads to down-regulation of neural border zone, neural crest and cranial placode genes, and concomitant expansion of neural plate genes. Gain-of-function leads to a broader neural border zone, expanded neural crest and altered cranial placode domains. In loss-of-function assays, the later developing otocyst is reduced in size, which impacts gene expression. In contrast, the size of the otocyst in gain-of-function assays is not changed but the expression domains of several otocyst genes are reduced. Together these findings establish an interaction between Pa2G4 and Six1, and demonstrate that it has an important role in the development of tissues affected in BOS. Thereby, we suggest that pa2g4 is a potential candidate gene for BOS.

PubMed ID: 27940157
PMC ID: PMC5221411
Article link: Dev Biol
Grant support: [+]
Genes referenced: ctrl dlx5 eya1 foxd3 foxd4l1.1 irx1 msx1 myc otx2 pa2g4 pax2 pax3 six1 sox11 sox2 sox9 tbx1 tfap2a zic2
GO keywords: neural crest cell development [+]
Morpholinos: pa2g4 MO3 pa2g4 MO4

Disease Ontology terms: branchiootorenal syndrome
OMIMs: BRANCHIOOTORENAL SYNDROME 1; BOR1 [+]

Article Images: [+] show captions
References:
Anderson, 2014, Pubmed [+]


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