Genomes and Genes
Gene Symbol: pcdh8
Description: protocadherin 8
Alias: papc, zPAPC, protocadherin-8, paraxial protocadherin
- Zhu S, Liu L, Korzh V, Gong Z, Low B. RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling. Cell Signal. 2006;18:359-72 pubmed..These findings also support the versatility of the zebrafish as a model to further investigate the roles of various classes of small GTPases in regulating cell dynamics in vivo. ..
- Coyle R, Latimer A, Jessen J. Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: evidence for an interaction with non-canonical Wnt signaling. Exp Cell Res. 2008;314:2150-62 pubmed publisher..Together, our results support the notion that pathways regulating pericellular proteolysis and cell polarity converge to promote efficient cell migration. ..
- Dill K, Amacher S. tortuga refines Notch pathway gene expression in the zebrafish presomitic mesoderm at the post-transcriptional level. Dev Biol. 2005;287:225-36 pubmed
- Henry C, Poage C, McCarthy M, Campos Ortega J, Cooper M. Regionally autonomous segmentation within zebrafish presomitic mesoderm. Zebrafish. 2005;2:7-18 pubmed publisher..Furthermore, expression patterns of deltaD, paraxial protocadherin C (papc), and myoD within recently formed somites also appear to be relatively unperturbed by either ..
- Tawk M, Araya C, Lyons D, Reugels A, Girdler G, Bayley P, et al. A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis. Nature. 2007;446:797-800 pubmed
- Dosch R, Wagner D, Mintzer K, Runke G, Wiemelt A, Mullins M. Maternal control of vertebrate development before the midblastula transition: mutants from the zebrafish I. Dev Cell. 2004;6:771-80 pubmed..These mutants exhibit phenotypes not previously observed in zygotic mutant screens. This collection of maternal-effect mutants provides the basis for a molecular genetic analysis of the maternal control of embryogenesis in vertebrates. ..
- Nikaido M, Law E, Kelsh R. A systematic survey of expression and function of zebrafish frizzled genes. PLoS ONE. 2013;8:e54833 pubmed publisher..Furthermore, we show that the two fzd7 genes function together with fzd10 to regulate epiboly movements and mesoderm differentiation. ..
- McFarland K, Warga R, Kane D. Genetic locus half baked is necessary for morphogenesis of the ectoderm. Dev Dyn. 2005;233:390-406 pubmed
- Mizoguchi T, Izawa T, Kuroiwa A, Kikuchi Y. Fgf signaling negatively regulates Nodal-dependent endoderm induction in zebrafish. Dev Biol. 2006;300:612-22 pubmed..Altogether, these results suggest that Fgf signaling negatively regulates endoderm induction, possibly through repression of cas expression and down-regulation of Cas function. ..
- Ramel M, Buckles G, Lekven A. Conservation of structure and functional divergence of duplicated Wnt8s in pufferfish. Dev Dyn. 2004;231:441-8 pubmed publisher..This finding suggests that zebrafish (and possibly teleost in general) Wnt8 receptors are able to discriminate between highly related ligands...
- Yao S, Xie L, Qian M, Yang H, Zhou L, Zhou Q, et al. Pnas4 is a novel regulator for convergence and extension during vertebrate gastrulation. FEBS Lett. 2008;582:2325-32 pubmed publisher..In addition, genetic interaction assays indicate that Pnas4 might act in parallel with non-canonical Wnt signal in the regulation of cell movement. Our data suggest that Pnas4 is a key regulator of cell movement during gastrulation. ..
- Machingo Q, Fritz A, Shur B. A beta1,4-galactosyltransferase is required for convergent extension movements in zebrafish. Dev Biol. 2006;297:471-82 pubmed
- Oates A, Bruce A, Ho R. Too much interference: injection of double-stranded RNA has nonspecific effects in the zebrafish embryo. Dev Biol. 2000;224:20-8 pubmed..mRNAs from the papc, tbx6, and gata1 genes, which depend on tbx16/spt function for their expression, were reduced, apparently mimicking ..
- Londin E, Niemiec J, Sirotkin H. Chordin, FGF signaling, and mesodermal factors cooperate in zebrafish neural induction. Dev Biol. 2005;279:1-19 pubmed..Our results support a model in which specification of anterior neural tissue requires early FGF-mediated repression of BMP transcript levels and later activities of Chordin and mesodermal factors. ..
- Li L, Chen D, Li J, Wang X, Wang N, Xu C, et al. Aggf1 acts at the top of the genetic regulatory hierarchy in specification of hemangioblasts in zebrafish. Blood. 2014;123:501-8 pubmed publisher..Taken together, these data indicate that aggf1 is involved in differentiation of both hematopoietic and endothelial lineages and that aggf1 acts upstream of scl, fli1, and etsrp in specification of hemangioblasts. ..
- He Y, Xu X, Zhao S, Ma S, Sun L, Liu Z, et al. Maternal control of axial-paraxial mesoderm patterning via direct transcriptional repression in zebrafish. Dev Biol. 2014;386:96-110 pubmed publisher..These results demonstrated that direct transcriptional repression of the decisive axial mesoderm gene by maternal ventralizing factor is a crucial regulatory mechanism of initiating axial-paraxial mesoderm patterning in vertebrates. ..
- Plaster N, Sonntag C, Schilling T, Hammerschmidt M. REREa/Atrophin-2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development. Dev Dyn. 2007;236:1891-904 pubmed..We present a model for RERE-dependent patterning in which tissue-specific transcriptional repression, by means of an REREa-HDAC complex, modulates growth factor signaling during embryogenesis. ..
- Kawamura A, Koshida S, Hijikata H, Sakaguchi T, Kondoh H, Takada S. Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites. Genes Dev. 2005;19:1156-61 pubmed..Furthermore, Her13.2 augments autorepression of her1 in association with Her1 protein. Therefore, FGF signaling appears to maintain the oscillation machinery by supplying a binding partner, Her13.2, for Her1. ..
- Oates A, Mueller C, Ho R. Cooperative function of deltaC and her7 in anterior segment formation. Dev Biol. 2005;280:133-49 pubmed..Thus, anterior segmentation requires the functions of both her and delta family members in a parallel manner, suggesting that the segmentation oscillator operates in paraxial mesoderm along the entire vertebrate axis. ..
- Kawamura A, Koshida S, Hijikata H, Ohbayashi A, Kondoh H, Takada S. Groucho-associated transcriptional repressor ripply1 is required for proper transition from the presomitic mesoderm to somites. Dev Cell. 2005;9:735-44 pubmed..Thus, ripply1 plays dual roles in the transition from the PSM to somites: termination of the segmentation program in the PSM and maintenance of the rostrocaudal polarity. ..
- Harrington M, Hong E, Fasanmi O, Brewster R. Cadherin-mediated adhesion regulates posterior body formation. BMC Dev Biol. 2007;7:130 pubmed..These findings further highlight the central role that adhesion molecules play in the cellular rearrangements that drive morphogenesis in vertebrates and identify classical cadherins as major contributors to tail development. ..
- Yamashita S, Miyagi C, Fukada T, Kagara N, Che Y, Hirano T. Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer. Nature. 2004;429:298-302 pubmed..Furthermore, we demonstrate that LIV1 is essential for the nuclear localization of zinc-finger protein Snail, a master regulator of EMT. These results establish a molecular link between STAT3, LIV1 and Snail in EMT. ..
- O Neill K, Thorpe C. BMP signaling and spadetail regulate exit of muscle precursors from the zebrafish tailbud. Dev Biol. 2013;375:117-27 pubmed publisher..They also elucidate that chd;spt tailbud mesodermal progenitor cells (MPC) behave autonomously and their dynamics within the tailbud are drastically different than WT MPCs. ..
- Barrios A, Poole R, Durbin L, Brennan C, Holder N, Wilson S. Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis. Curr Biol. 2003;13:1571-82 pubmed..We propose a new role for Eph receptors and Ephrins as intercellular signaling molecules that establish cell polarity during mesenchymal-to-epithelial transition of the paraxial mesoderm. ..
- Khan A, Nakamoto A, Okamoto S, Tai M, Nakayama Y, Kobayashi K, et al. Pou2, a class V POU-type transcription factor in zebrafish, regulates dorsoventral patterning and convergent extension movement at different blastula stages. Mech Dev. 2012;129:219-35 pubmed publisher..Collectively, these data demonstrated that pou2 regulates DV patterning and CE movement in zebrafish embryos at the midblastula and late blastula stages, respectively...
- Schwend T, Loucks E, Snyder D, Ahlgren S. Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish. J Lipid Res. 2011;52:1328-44 pubmed publisher..Collectively, these studies show that npc1 is required early for proper cell movement and cholesterol localization and later for cell survival. ..
- Snow C, Peterson M, Khalil A, Henry C. Muscle development is disrupted in zebrafish embryos deficient for fibronectin. Dev Dyn. 2008;237:2542-53 pubmed publisher..Fast- and slow-twitch muscle lengths are also more frequently uncoupled. These data suggest that fn may function to regulate fiber organization and limit fast-twitch muscle fiber length. ..
- Jayashankar V, Nguyen M, Carr B, Zheng D, Rosales J, Rosales J, et al. Protein phosphatase 1 ? paralogs encode the zebrafish myosin phosphatase catalytic subunit. PLoS ONE. 2013;8:e75766 pubmed publisher..In addition, both genes are required for convergence and extension during gastrulation and correct dosage of the protein products is required. ..
- Pasini A, Jiang Y, Wilkinson D. Two zebrafish Notch-dependent hairy/Enhancer-of-split-related genes, her6 and her4, are required to maintain the coordination of cyclic gene expression in the presomitic mesoderm. Development. 2004;131:1529-41 pubmed
- Warga R, Kane D. A role for N-cadherin in mesodermal morphogenesis during gastrulation. Dev Biol. 2007;310:211-25 pubmed..Hence, besides a well-established role in neural and somite morphogenesis, N-cadherin is essential for morphogenesis of the mesodermal germ layer during gastrulation. ..
- Muyskens J, Kimmel C. Tbx16 cooperates with Wnt11 in assembling the zebrafish organizer. Mech Dev. 2007;124:35-42 pubmed..in embryos with reduced function of the T-box transcription factor Tbx16 (Spadetail) or its genetic target paraxial protocadherin (Papc), synchrony is lost, coalesence is disrupted, and the midline domain is misshaped...
- Griffin K, Kimelman D. One-Eyed Pinhead and Spadetail are essential for heart and somite formation. Nat Cell Biol. 2002;4:821-5 pubmed..We propose that the major role of Spt in somitogenesis is to promote the differentiation of presomitic mesoderm from tailbud progenitors by antagonizing progenitor-type gene expression and behaviour. ..
- Vervenne H, Crombez K, Lambaerts K, Carvalho L, Köppen M, Heisenberg C, et al. Lpp is involved in Wnt/PCP signaling and acts together with Scrib to mediate convergence and extension movements during zebrafish gastrulation. Dev Biol. 2008;320:267-77 pubmed publisher..Finally, we demonstrate that Lpp interacts with the PCP protein Scrib in zebrafish, and that Lpp and Scrib cooperate for the mediation of C&E. ..
- Akanuma T, Koshida S, Kawamura A, Kishimoto Y, Takada S. Paf1 complex homologues are required for Notch-regulated transcription during somite segmentation. EMBO Rep. 2007;8:858-63 pubmed..Therefore, zebrafish homologues of the yeast Paf1 complex seem to preferentially affect a subset of genes, including Notch-regulated genes, during embryogenesis. ..
- Challa A, McWhorter M, Wang C, Seeger M, Beattie C. Robo3 isoforms have distinct roles during zebrafish development. Mech Dev. 2005;122:1073-86 pubmed..This study reveals a novel function for Robo receptors in specifying ventral cell fates during vertebrate development. ..
- Sawada A, Fritz A, Jiang Y, Yamamoto A, Yamasu K, Kuroiwa A, et al. Zebrafish Mesp family genes, mesp-a and mesp-b are segmentally expressed in the presomitic mesoderm, and Mesp-b confers the anterior identity to the developing somites. Development. 2000;127:1691-702 pubmed..in expression of the posterior genes, myoD and notch5, with uniform expression of the anterior genes, FGFR1, papc and notch6...
- Kilian B, Mansukoski H, Barbosa F, Ulrich F, Tada M, Heisenberg C. The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech Dev. 2003;120:467-76 pubmed..The characterisation of the role of Ppt/Wnt5 provides insight into the functional diversity of Wnt genes in regulating vertebrate gastrulation movements. ..
- Wylie A, Fleming J, Whitener A, Lekven A. Post-transcriptional regulation of wnt8a is essential to zebrafish axis development. Dev Biol. 2014;386:53-63 pubmed publisher..Thus, post-transcriptional control of wnt8a is essential to fine tune the balance of the signaling outputs of the complex wnt8a locus. ..
- Yabe T, Takada S. Mesogenin causes embryonic mesoderm progenitors to differentiate during development of zebrafish tail somites. Dev Biol. 2012;370:213-22 pubmed publisher..Based on these results, we speculate that msgn1 expression in association with that of ntl may allow the differentiation of progenitor cells to proceed during development of somites in the tail...
- Oates A, Rohde L, Ho R. Generation of segment polarity in the paraxial mesoderm of the zebrafish through a T-box-dependent inductive event. Dev Biol. 2005;283:204-14 pubmed
- Hao H, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012;485:195-200 pubmed publisher..These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration...
- Kok F, Shepherd I, Sirotkin H. Churchill and Sip1a repress fibroblast growth factor signaling during zebrafish somitogenesis. Dev Dyn. 2010;239:548-58 pubmed publisher..Finally, we found that blocking FGF8 restores somite morphology in ChCh and Sip1a compromised embryos. These results demonstrate a novel role for ChCh and Sip1a in repression of FGF activity. ..
- Liu X, Ning G, Meng A, Wang Q. MicroRNA-206 regulates cell movements during zebrafish gastrulation by targeting prickle1a and regulating c-Jun N-terminal kinase 2 phosphorylation. Mol Cell Biol. 2012;32:2934-42 pubmed publisher..Therefore, mir206 is an essential, novel regulator for normal convergent and extension movements by regulating mitogen-activated protein kinase (MAPK) JNK signaling. ..
- Joshi P, Liang J, DiMonte K, Sullivan J, Pimplikar S. Amyloid precursor protein is required for convergent-extension movements during Zebrafish development. Dev Biol. 2009;335:1-11 pubmed publisher..Collectively, this work demonstrates that the zebrafish model is a powerful system to define the role of APP during embryonic development and to evaluate the functional activity of fAD mutant APP. ..
- Lee H, Tseng W, Lo F, Liu T, Tsai H. FoxD5 mediates anterior-posterior polarity through upstream modulator Fgf signaling during zebrafish somitogenesis. Dev Biol. 2009;336:232-45 pubmed publisher..An Fgf-FoxD5-Mesps signaling network is therefore proposed. ..
- Yao S, Qian M, Deng S, Xie L, Yang H, Xiao C, et al. Kzp controls canonical Wnt8 signaling to modulate dorsoventral patterning during zebrafish gastrulation. J Biol Chem. 2010;285:42086-96 pubmed publisher..Thus, our results provide the first insight into the mechanism involved in the initiation of zygotic canonical Wnt signals by a maternally derived transcription factor. ..
- Guo L, Yamashita H, Kou I, Takimoto A, Meguro Horike M, Horike S, et al. Functional Investigation of a Non-coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation. PLoS Genet. 2016;12:e1005802 pubmed publisher..Thus, our study presents a novel pathological feature of LBX1 and its zebrafish homologs in body axis deformation at various stages of embryonic and subsequent growth in zebrafish. ..
- Chen Q, Takada R, Takada S. Loss of Porcupine impairs convergent extension during gastrulation in zebrafish. J Cell Sci. 2012;125:2224-34 pubmed publisher..Thus, a decrease of Porcn activity does not equivalently affect trafficking and lipidation of different Wnt proteins in zebrafish embryos and in cultured mammalian cells. ..
- Kok F, Oster E, Mentzer L, Hsieh J, Henry C, Sirotkin H. The role of the SPT6 chromatin remodeling factor in zebrafish embryogenesis. Dev Biol. 2007;307:214-26 pubmed..However, additional Spt6 mutant phenotypes are likely caused by vital functions of Spt6 in other pathways. ..
- Blanco M, Barrallo Gimeno A, Acloque H, Reyes A, Tada M, Allende M, et al. Snail1a and Snail1b cooperate in the anterior migration of the axial mesendoderm in the zebrafish embryo. Development. 2007;134:4073-81 pubmed
- Row R, Maître J, Martin B, Stockinger P, Heisenberg C, Kimelman D. Completion of the epithelial to mesenchymal transition in zebrafish mesoderm requires Spadetail. Dev Biol. 2011;354:102-10 pubmed publisher..This mutation creates an ideal system for dissecting the specific properties of cells undergoing the morphological transition of maturing mesoderm, as we demonstrate with a direct measurement of cell-cell adhesion. ..
- Retnoaji B, Akiyama R, Matta T, Bessho Y, Matsui T. Retinoic acid controls proper head-to-trunk linkage in zebrafish by regulating an anteroposterior somitogenetic rate difference. Development. 2014;141:158-65 pubmed publisher..Overall, our results indicate that RA regulation of the AP difference is crucial for proper linkage between the head and trunk in the vertebrate body plan. ..
- Aerne B, Ish Horowicz D. Receptor tyrosine phosphatase psi is required for Delta/Notch signalling and cyclic gene expression in the presomitic mesoderm. Development. 2004;131:3391-9 pubmed..Impairing RPTPpsi activity also interferes with convergent extension during gastrulation. We discuss this dual requirement for RPTPpsi in terms of potential functions in Notch and Wnt signalling. ..
- Li X, Roszko I, Sepich D, Ni M, Hamm H, Marlow F, et al. Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development. 2013;140:3028-39 pubmed publisher..Our study reveals a role for Gpr125 in PCP-mediated processes and provides mechanistic insight into Wnt/PCP signaling. ..
- Lim C, Chong S, Jiang Y. Udu deficiency activates DNA damage checkpoint. Mol Biol Cell. 2009;20:4183-93 pubmed publisher..Furthermore, Udu is colocalized with 5-bromo-2'-deoxyuridine and heterochromatin during DNA replication, suggesting a role in maintaining genome integrity. ..
- Hong S, Dawid I. FGF-dependent left-right asymmetry patterning in zebrafish is mediated by Ier2 and Fibp1. Proc Natl Acad Sci U S A. 2009;106:2230-5 pubmed publisher..We conclude that Ier2 and Fibp1 mediate FGF signaling in ciliogenesis in Kupffer's Vesicle and in the establishment of laterality in the zebrafish embryo. ..
- Skouloudaki K, Puetz M, Simons M, Courbard J, Boehlke C, Hartleben B, et al. Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development. Proc Natl Acad Sci U S A. 2009;106:8579-84 pubmed publisher..We hypothesize that Hippo signaling is required for normal pronephros development in zebrafish and that Scribble is a candidate link between Fat and the Hippo signaling cascade in vertebrates. ..
- Komoike Y, Kawamura A, Shindo N, Sato C, Satoh J, Shiurba R, et al. Zebrafish Polycomb group gene ph2alpha is required for epiboly and tailbud formation acting downstream of FGF signaling. Biochem Biophys Res Commun. 2005;328:858-66 pubmed..In addition, cells expressing mRNAs for no tail, spadetail, myoD, and papc, which are involved in FGF-related development of posterior mesoderm, were distributed abnormally...
- Gebruers E, Cordero Maldonado M, Gray A, Clements C, Harvey A, Edrada Ebel R, et al. A phenotypic screen in zebrafish identifies a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling. PLoS ONE. 2013;8:e83293 pubmed publisher..Further investigation of pCAME's mechanism of action will help determine this compound's pharmacological utility...
- Kai M, Ueno N, Kinoshita N. Phosphorylation-dependent ubiquitination of paraxial protocadherin (PAPC) controls gastrulation cell movements. PLoS ONE. 2015;10:e0115111 pubmed publisherb>Paraxial protocadherin (PAPC) has been shown to be involved in gastrulation cell movements during early embryogenesis...
- Tian J, Ling L, Shboul M, Lee H, O CONNOR B, Merriman B, et al. Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling. Am J Hum Genet. 2010;87:768-78 pubmed publisher..We conclude that CHSY1 is a secreted FRINGE enzyme required for adjustment of NOTCH signaling throughout human and fish embryogenesis and particularly during limb patterning. ..
- Esguerra C, Nelles L, Vermeire L, Ibrahimi A, Crawford A, Derua R, et al. Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination. Development. 2007;134:4381-93 pubmed
- Ishimatsu K, Takamatsu A, Takeda H. Emergence of traveling waves in the zebrafish segmentation clock. Development. 2010;137:1595-9 pubmed publisher..Furthermore, we suggest that Fgf has an essential role in establishing the period gradient that is required for the her1 spatial oscillation pattern at the emergence of the traveling wave...
- Pei W, Noushmehr H, Costa J, Ouspenskaia M, Elkahloun A, Feldman B. An early requirement for maternal FoxH1 during zebrafish gastrulation. Dev Biol. 2007;310:10-22 pubmed..Our studies thus point to an essential role for maternal FoxH1 and downstream keratins during gastrulation that is epistatic to Nodal signaling. ..
- Young T, Poobalan Y, Tan E, Tao S, Ong S, Wehner P, et al. The PDZ domain protein Mcc is a novel effector of non-canonical Wnt signaling during convergence and extension in zebrafish. Development. 2014;141:3505-16 pubmed publisher..Taken together, our results identify Mcc as a novel intracellular effector of non-canonical Wnt5b/Vangl2/Ror2 signaling during vertebrate gastrulation. ..
- Holley S, Takeda H. Catching a wave: the oscillator and wavefront that create the zebrafish somite. Semin Cell Dev Biol. 2002;13:481-8 pubmed
- Lou Q, He J, Hu L, Yin Z. Role of lbx2 in the noncanonical Wnt signaling pathway for convergence and extension movements and hypaxial myogenesis in zebrafish. Biochim Biophys Acta. 2012;1823:1024-32 pubmed publisher..Our results suggest that the key noncanonical Wnt signaling components Wnt5, Dvl, and RhoA are downstream effectors involved in the regulative roles of lbx2 in CE movement and hypaxial myogenesis during zebrafish embryogenesis. ..
- Babb S, Marrs J. E-cadherin regulates cell movements and tissue formation in early zebrafish embryos. Dev Dyn. 2004;230:263-77 pubmed..E-cadherin mRNA coinjection demonstrated the specificity of cdh1 MO-induced defects. Our experiments illustrate the importance of cdh1 in regulating morphogenetic cell movements and tissue formation in the early embryo. ..
- Rhinn M, Lun K, Amores A, Yan Y, Postlethwait J, Brand M. Cloning, expression and relationship of zebrafish gbx1 and gbx2 genes to Fgf signaling. Mech Dev. 2003;120:919-36 pubmed..Moreover, our results provide an example for switching of a specific gene function of gbx1 versus gbx2 between orthologous genes in zebrafish and mammals. ..