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Expression of Avian Prickle Genes During Early Development and Organogenesis

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Expression of Avian Prickle Genes During Early Development and Organogenesis DEVELOPMENTAL DYNAMICS 237:1442–1448, 2008 PATTERNS & PHENOTYPES Expression of Avian prickle Genes During Early Development and Organogenesis Oliver Cooper,† Dylan Sweetman, Laura Wagstaff,‡ and Andrea Mu¨ nsterberg* Chicken homologues of prickle-1 (pk-1) and prickle-2 (pk-2) were isolated to gain insight into the extent of planar cell polarity signaling during avian embryogenesis. Bioinformatics analyses demonstrated homology and showed that pk-1 and pk-2 exhibited conserved synteny with ADAMTS20 and ADAMTS9, GON-related zinc metalloproteases. Expression of pk-1 and pk-2 was established during embryogenesis and early organogenesis, using in situ hybridization and sections of chicken embryos. At early stages, pk-1 was expressed in Hensen’s node, primitive streak, ventral neural tube, and foregut. In older embryos, pk-1 transcripts were detected in dorsolateral epithelial somites, dorsomedial lip of dermomyotomes, and differentiating myotomes. Furthermore, pk-1 expression was seen in lateral body folds, limb buds, and ventral metencephalon. pk-2 was expressed in Hensen’s node and neural ectoderm at early stages. In older embryos, pk-2 expression was restricted to ventromedial epithelial somites, except in the most recently formed somite pair, and limb bud mesenchyme. Developmental Dynamics 237:1442–1448, 2008. © 2008 Wiley-Liss, Inc. Key words: prickle; planar cell polarity; PCP; Primitive streak; Somite; Limb bud; ADAMTS Accepted 24 January 2008 INTRODUCTION extension movements and cell orienta- while pk function has been well char- tion in the inner ear (Carreira-Bar- acterized in the context of PCP sig- During invertebrate development, dif- bosa et al., 2003; Veeman et al., 2003; nals, it is becoming clear that pk ho- fusible ligands are interpreted by pla- Deans et al., 2007). Tissue responses mologues have functions beyond nar cell polarity (PCP) signaling to co- to pk-mediated PCP signals are ordinate morphogenetic events. In establishing PCP. For example, pk-1 ␤ Drosophila, PCP establishes the plane caused by a combination of polarized antagonizes Wnt/ -catenin signals in of cell orientation in the developing cytoskeletal and cell adhesion rear- vitro by targeting Dsh for degradation cuticle, eye, and wing by means of the rangements by means of the activities (Veeman et al., 2003; Chan et al., distal and proximal subcellular local- of Jun kinase, members of the Rho 2006). In addition, recent in vivo stud- ization of several key proteins, includ- family of small GTPases, and calcium ies have identified pk-1 as a regulator ing prickle (pk; Lawrence et al., 2007; signaling (Classen et al., 2005; Gibson of notch activity. In the Drosophila Seifert and Mlodzik, 2007). In the et al., 2006; Shimada et al., 2006; Le- eye, PCP signals form a feedback loop primitive chordate, Ciona savignyi, Pk cuit and Lenne, 2007; Slusarski and that regulates Notch and Delta signal- regulates cell intercalation of noto- Pelegri, 2007). ing (Cooper and Bray, 1999; Fanto chord cells (Jiang et al., 2005). Verte- The complete extent of PCP signal- and Mlodzik, 1999). The pk mutant, brate Pk homologues coordinate the ing during vertebrate development is pkpk/sple ectopically activates notch ac- morphogenetic events of convergent not well understood. Furthermore, tivity in the Drosophila eye (Strutt, School of Biological Sciences, University of East Anglia, Norwich, United Kingdom Grant sponsor: BBSRC DTA studentships; Grant sponsor: Wellcome Trust; Grant number: 070699; Grant sponsor: EU FP6 NoE MYORES; Grant number: LSHG-CT-2004-511978. †Dr. Cooper’s present address is Center for Neuroregeneration Research, Harvard Medical School, McLean Hospital, Belmont, MA 02478. ‡Dr. Wagstaff’s present address is Biomedical Research Centre, University of East Anglia, Norwich NR4 7TJ, UK. *Correspondence to: Andrea Mu¨ nsterberg, School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK. E-mail: [email protected] DOI 10.1002/dvdy.21490 Published online 25 March 2008 in Wiley InterScience (www.interscience.wiley.com). © 2008 Wiley-Liss, Inc. PRICKLE GENE EXPRESSION IN CHICK EMBRYOS 1443 Fig. 1. Comparison of pk-1 and pk-2 homologues. A: Alignment of the predicted amino acid sequence for the chicken pk-1 and pk-2 genes. PET (red), LIM (green), and PKH (blue) domains are indicated with consensus matches (black shade) for chick and human homologues of pk-1 and pk-2. B: A phylogenetic tree shows the degree of similarity of pk-1 and pk-2 human (hs), mouse (m), chicken (c), and zebrafish (zf) orthologues. 2002), and pk homologues facilitate (Gubb et al., 1999), there is currently et al., 1999). Emerging evidence sug- the nuclear translocation of charlatan/ no evidence from Northern blots or gests that the LIM motif is a hallmark NRSF/REST, a repressor of the Notch expressed sequence tag databases of proteins that associate with both ligand, Delta (Shimojo and Hersh, that vertebrate pk-1 or pk-2 are alter- the actin cytoskeleton and the tran- 2003; Shimojo and Hersh, 2006; natively spliced (Deans et al., 2007). scriptional machinery (Kadrmas and Tsuda et al., 2006). Based on the predicted protein se- Beckerle, 2004). The N-terminal PET During the first 4 days of chicken quences, chicken pk-1 and pk-2 encode domain combines with the three LIM development, the embryo undergoes 828 amino acid and 832 amino acid domains during interactions with extensive remodeling, both during proteins, respectively. Phylogenetic other proteins (Gubb et al., 1999). The the establishment of the three germ analyses revealed strong sequence PKH domain contains a CaaX-motif layers (ectoderm, mesoderm and similarities of chicken pk-1 with hu- prenylation site that determines pro- endoderm) and during tissue forma- man (88%) and zebrafish (64.3%) ho- tein–protein and protein–membrane tion. To investigate the possible ex- mologues. Similarly, chicken pk-2 had interactions (Desnoyers and Seabra, tent of prickle function in PCP and strong sequence similarity with hu- 1998; Maurer-Stroh et al., 2003). Bio- other signaling pathways, we exam- man (85.5%) and zebrafish (56.5%) ho- chemical and mutagenesis studies of ined the expression patterns of the mologues. In addition, our phyloge- PRICKLE1 and Drosophila pk have chicken pk homologues, pk-1 and pk-2 netic analyses indicated that the demonstrated that this CaaX motif is during this period of embryogenesis. identities of mouse pk-1 and pk-2 were a farnesylation that regulates nucle- interchanged and this was adjusted ar/nuclear membrane localization RESULTS AND DISCUSSION (Fig. 1; Table 1; Katoh and Katoh, (Shimojo and Hersh, 2003, 2006; Vee- 2003). man et al., 2003). To further charac- Comparison of Chicken pk-1 Structural analyses showed that terize the amino acid sequence of and pk-2 Proteins chicken pk-1 and pk-2 proteins are chicken pk-1, we used a transmem- Polymerase chain reaction (PCR) composed of an N-terminal PET do- brane topology prediction method primers were designed, using the En- main, three central LIM domains, and (MEMSAT3, http://bioinf.cs.ucl.ac.uk/ semblGenomeBrowser(www.ensembl. a C-terminal PKH domain. The LIM psipred/) (Jones et al., 1994). The org), to amplify the predicted coding motifs (Lin-11 Isl-1 Mec-3; InterPro method predicted a transmembrane sequences for the chicken homologues accession IPR001781) are cysteine- helical domain between 801 and 818 of pk-1 and pk-2 (see the Experimen- rich, contain zinc-binding protein do- amino acids of chicken pk-1, adjacent tal Procedures section). While Dro- mains and commonly mediate pro- to the CaaX motif within the PKH do- sophila pk is alternatively spliced to tein–protein interactions (Michelsen main. The prediction of a transmem- produce pk, pkM, and sple isoforms et al., 1993; Dawid et al., 1998; Gubb brane helical domain at the C-termi- 1444 COOPER ET AL. TABLE 1. Protein and cDNA Sequence Accession Numbers for prickle-1 and prickle-2 Gene Species Protein Accession NCBI and Ensembl cDNA Accession NCBI and Ensembl Prickle-1 Gallus gallus ENSGALP00000015542 ENSGALG00000009556 Prickle-1 Homo NP_694571.1 NM_153026 sapiens ENSP00000345064 ENSG00000139174 Prickle-1 Mus AAI17894 BC117893 (Predicted) musculus ENSMUSP00000049204 ENSMUSG00000030020 Prickle-1 Danio NP_899185 NM_183342.2 rerio ENSDARP00000059513 ENSDARG00000040649 Prickle-2 Gallus gallus ENSGALP00000011832 ENSGALG00000007332 Prickle-2 Homo NP_942559.1 NM_198859 sapiens ENSP00000295902 ENSG00000163637 Prickle-2 Mus AAI45755 NM_001033217.1 musculus ENSMUSP00000032093 ENSMUSG00000030020 Prickle-2 Danio NP_899186.1 NM_183343 rerio ENSDARP00000054743 ENSDARG00000037593 nus of chicken pk-1 suggests that the taken together, bioinformatic analy- (PRICKLE2) and F1 of mouse chromo- protein can function as an integral ses of chicken pk-1 and pk-2 indicate some 15 (Prickle2). protein. Four other C-terminal do- that the N-termini bind to protein tar- Of interest, chicken pk-1 and pk-2 mains of PRICKLE1 regulate protein gets, while the C-termini regulate the shared similar PET/LIM domains and localization (Shimojo and Hersh, localization of the putative protein synteny with chicken testin (ENS- 2006). We used bioinformatics to con- complex. GALG00000009398; NP_989954.1) firm that these domains were con- and chicken dyxin/LMCD1 (ENS- served in chicken pk-1 and pk-2 Genomic Organization of GALG00000008349). Testin associ- (www.psort.org) (Zhou et al., 2004; ates with the cytoskeleton, whereas Chicken pk-1 and pk-2 Xue et al., 2005). In addition, chicken dyxin acts as a transcriptional cofac- pk-1 contained three predicted nu- To characterize the chicken pk homo- tor. Neither protein contains a PKH clear localization signals (NLS) and a logues further, the genomic organiza- domain (Katoh and Katoh, 2003; cyclic AMP-dependent protein kinase tion of these two genes was examined. Drusco et al., 2005; Rath et al., 2005). A (PKA) phosphorylation site, which Chicken pk-1 was located on contig Immediately upstream of pk-1 and were conserved with PRICKLE1. 6.521 of chromosome 1 and was syn- pk-2 in the chicken genome were AD- However, chicken pk-2 contained only tenic with q12 of human chromosome AMTS20 and ADAMTS9.
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