Expression of the fras1/frem gene family during zebrafish development and fin morphogenesis

Abstract

Mouse studies have highlighted the requirement of the extracellular matrix Fras and Frem proteins for embryonic epidermal adhesion. Mutations of the genes encoding some of these proteins underlie the blebs mouse mutants, whereas mutations in human FRAS1 and FREM2 cause Fraser syndrome, a congenital disorder characterized by embryonic blistering and renal defects. We have cloned the zebrafish homologues of these genes and characterized their evolutionary diversification and expression during development. The fish gene complement includes fras1, frem1a, frem1b, frem2a, frem2b, and frem3, which display complex overlapping and complementary expression patterns in developing tissues including the pharyngeal arches, hypochord, musculature, and otic vesicle. Expression during fin development delineates distinct populations of epidermal cells which have previously only been described at a morphological level. We detect relatively little gene expression in epidermis or pronephros, suggesting that the essential role of these proteins in mediating their development in humans and mice is recently evolved. Developmental Dynamics 237:3295-3304, 2008.

Pharyngeal morphogenesis requires fras1 - itga8 -dependent epithelial-mesenchymal interaction

“…Consistent with previous reports (Carney et al, 2010; Gautier et al, 2008; Talbot et al, 2012; Westcot et al, 2015), fras1 transcript is prominently expressed in ectoderm and endoderm lining pharyngeal arches (Fig. 4A, B).…”

“…The epithelially-expressed gene Fras1 (Gautier et al, 2008; McGregor et al, 2003; Vrontou et al, 2003) and the mesenchymally-expressed gene Integrin alpha8 ( Itga8 ) (Benjamin et al, 2009; Schnapp et al, 1995a) are each thought to mediate epithelial-mesenchymal interactions (Smyth and Scambler, 2005). Mammalian Itga8 is a transmembrane protein involved in cell adhesion (Schnapp et al, 1995b) and signaling (Linton et al, 2007; Pitera et al, 2012).…”

Mechanism of pectoral fin outgrowth in zebrafish development

“…Interestingly, rspo2 is crucial for AER maintenance, and rspo2 knockout mice have limb defects (lack of fibula or distal phalangeal bones) (Nam et al, 2007;Aoki et al, 2008), but the functions of the rspo2 gene in fin development remain unknown. Regarding another dAF signal, Gautier et al (Gautier et al, 2008) showed that some members of fras1/frem gene family are expressed in the distal margin of the pectoral fin bud. We examined the expression of these genes and found that frem2a expression was stronger in the dAF than in the pAF (Yano and Tamura, 2012).…”

fras1shapes endodermal pouch 1 and stabilizes zebrafish pharyngeal skeletal development

“…Slavotinek and Tifft, 2002), severe epithelial defects are present in Fras1 mutant mice (McGregor et al, 2003;Vrontou et al, 2003) and fras1 mutant zebrafish (Carney et al, 2010). In mouse (McGregor et al, 2003;Vrontou et al, 2003) and zebrafish (Gautier et al, 2008), Fras1/fras1 mRNA is expressed by epithelial cells, including endoderm and ectoderm lining the pharyngeal arches. Fras1 encodes a transmembrane protein containing motifs implicated in signaling and adhesion (Gautier et al, 2008;McGregor et al, 2003).…”

“…In mouse (McGregor et al, 2003;Vrontou et al, 2003) and zebrafish (Gautier et al, 2008), Fras1/fras1 mRNA is expressed by epithelial cells, including endoderm and ectoderm lining the pharyngeal arches. Fras1 encodes a transmembrane protein containing motifs implicated in signaling and adhesion (Gautier et al, 2008;McGregor et al, 2003). The large extracellular portion of Fras1 is cleaved and released into basal lamina underlying epithelia (Carney et al, 2010;Chiotaki et al, 2007;Kiyozumi et al, 2006;.…”