Comparative expression study of sipa family members during early Xenopus laevis development

Abstract

The signal-induced proliferation-associated (SIPA) protein family belongs to the RapGAP protein superfamily. Previous studies mainly focused on the expression and function of SIPA genes in vertebrate neuronal tissue. Only limited data about the embryonic expression pattern of the genes are currently available. Our study provides the first expression analysis of sipa1, sipa1l1, sipa1l2, and sipa1l3 during early development of the vertebrate organism Xenopus laevis. In silico, analysis revealed that all genes are highly conserved across species. Semi-quantitative RT-PCR experiments demonstrated that the RNA of all genes was maternally supplied. By whole mount in situ hybridization approaches, we showed that sipa1 is mainly expressed in various sensory organs, the respiratory and blood system, heart, neural tube, and eye. In contrast, sipa1l1 showed a broad expression during development in particular within the brain, somites, eye, and heart. Sipa1l2 was detected in the branchial arches, glomerulus, and the developing eye. In contrast, sipa1l3 revealed a tissue specific expression within the olfactory and otic vesicles, the cranial placodes and ganglia, neural tube, pronephros, retina, and lens. In summary, all sipa gene family members are expressed throughout the whole developing Xenopus organism and might play an important role during vertebrate early embryogenesis.

An Epha4/Sipa1l3/Wnt pathway regulates eye development and lens maturation

“…In a previous study, we confirmed the genomic conservation of the sipa1l3 gene across species (Dolnik et al, 2016). Here, we showed a similar expression and function of Sipa1l3 in Xenopus compared with mouse and zebrafish (Greenlees et al, 2015;Lachke et al, 2012;Rothe et al, 2016). Consistent with the mouse model and human patients (Evers et al, 2015;Greenlees et al, 2015), eye and lens sizes were significantly reduced in Sipa1l3-deficient Xenopus embryos.…”

“…First, we determined the spatiotemporal expression pattern of sipa1l3 using an antisense RNA probe. As we have shown previously (Rothe et al, 2016) and as observed in mouse and zebrafish (Greenlees et al, 2015;Lachke et al, 2012), sipa1l3 transcripts were clearly detectable in the developing Xenopus eye including the early anterior neural plate where the eye field is localized (Fig. 1A, upper row, white arrowheads).…”

“…Besides its expression in neurons of the brain, Sipa1l3 is highly expressed in the mouse (Lachke et al, 2012), frog (this study and Rothe et al, 2016) and zebrafish (Greenlees et al, 2015) eye including in the retina and lens. Expression of the classically neuronal Sipa1l3 in lens tissue is not surprising considering the common origin of the retina and the lens in the ectoderm of the early embryo.…”

“…Besides its expression in the rodent brain, Sipa1l3 is also localized in the developing eye in humans, mice, frog and zebrafish, especially within the lens (Evers et al, 2015;Greenlees et al, 2015;Lachke et al, 2012;Rothe et al, 2016). In 2015, two groups independently showed that mutations of the human SIPA1L3 gene are related to congenital cataracts.…”

Knockdown of SIPA1L3 Inhibits the Proliferation and Invasion of Non–Small Cell Lung Cancer Cells Through the Hippo Pathway

“…All SIPA family members share common domains, namely an N-terminal Rap GAP domain (Rap-GTPase activating domain), a PDZ domain and a C-terminal coiled-coil domain carrying a leucin-zipper motif. SIPA1L1-SIPA1L3 contains an additional domain of unknown function (DUF3401) [6][7][8]. Base on its functional structure, we hypothesized that SIPA1L3 play an important functional role in lung cancer development.…”