Biochemical and Biophysical Research Communications
Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling
Section snippets
Materials and methods
Targeting vector construction and genotyping. The targeting vector was constructed by replacing exon 2 of the Sprouty4 gene with a PGK-Neo cassette, preserving the 5.0 kb (left arm) and 1.7 kb (right arm) of the homologous flanking sequences (Fig. S1A). Genotyping was done by using genomic PCR with primers (WT: 5′-GCAAGGAGTCAGGTAGCTGTAAGTGGAGTG-3′/5′-CCAAAGTGCAACCTGCCACTGGGTCAGCTG-3′ and Sprouty4 KO: 5′-GACCCTGGGTGAAGCTCCCAGGCTTCTTAG-3′/5′-TGCTAAAGCGCATGCTCCAGACTGCCTTGG-3′). Mice were backcrossed
Generation of Sprouty4 KO mice
To determine the function of Sprouty4 in the physiological state, mice lacking Sprouty4 gene were generated by homologous recombination. Disruption of Sprouty4 in embryonic stem cells was achieved by replacing exon 2 of the Sprouty4 gene with a PGK-Neo cassette (Fig. S1A). Successful recombination was ascertained by Southern blotting of murine tails using the indicated probe (Fig. S1B). The complete lack of functional transcripts and proteins in the Sprouty4 KO mice was confirmed by RT-PCR and
Acknowledgments
We thank T. Yoshioka, H. Fujii, N. Kinoshita, M. Ohtsu, Y. Yamada for technical assistance, and Ms. Y. Nishi for manuscript preparation. This work was supported by special Grants-in-aid from the Ministry of Education, Science, Technology, Sports, and Culture of Japan.
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2019, Developmental BiologyCitation Excerpt :The first member of the Sprouty family was found in a screen for genes involved in development of trachea and eyes in Drosophila (Casci et al., 1999; Hacohen et al., 1998). Like Drosophila Sprouty, mammalian Sprouty proteins antagonize FGF signaling in tubular morphogenesis associated with tracheal/lung development (Fig. 3A, A') (Metzger et al., 2008; Shaw et al., 2007; Tefft et al., 1999) and angiogenesis (Taniguchi et al., 2007a, 2009). Since these initial findings, the number of pathways and biological processes regulated by Sprouty proteins continues to expand, including submandibular parasympathetic gangliogenesis (Fig. 3B, B') (Knosp et al., 2015), ureteric branching (Fig. 3C, C') (Basson et al., 2005, 2006; Chi et al., 2004; Gross et al., 2003; Michos et al., 2010), external genitalia development (Fig. 3D, D') (Ching et al., 2014), endochondral bone formation (Fig. 3E, E') (Joo et al., 2016; Minowada et al., 1999), and branchial nerve development (Fig. 3F, F'') (Simrick et al., 2011), among others (Supplemental Table 1).