ZFIN ID: ZDB-PERS-010612-1
Crump, Gage DeKoeyer
Email: gcrump@usc.edu
URL: http://crumplab.usc.edu/
Affiliation: Crump Lab
Address: Center for Stem Cell and Regenerative Medicine USC Keck School of Medicine 1501 San Pablo St., ZNI 519/25 Los Angeles, CA 90033 USA
Country: United States
Phone: 323.442.2693
Fax: 323.442.4040
Orcid ID:

Vertebrates come in a dazzling array of shapes and sizes, their outward appearances largely determined by their skeletons. The facial skeleton in particular has undergone remarkable diversification, from the long trunks of elephants to the razor sharp jaws of sharks. Yet this menagerie of forms arises from very similar looking structures, called “pharyngeal arches”, in the embryos of all vertebrates. How then do these cells organize into the facial features appropriate for each animal? This question is fundamental for understanding not only how animal diversity is generated but also why development goes awry in human birth defects affecting the face.

The cartilages and bones that form the facial skeleton develop from a vertebrate-specific population of “crest” cells that form a series of pharyngeal arches. My laboratory studies the cellular basis of skeletal shaping in zebrafish because their embryos are transparent and develop rapidly, thus allowing us to directly observe development in living animals. By making high-resolution time-lapse recordings of transgenic zebrafish, in which a green fluorescent protein has been engineered specifically into skeletal precursor cells, we have pinpointed where in the arches the cells originate that make different cartilage elements.

We have also identified several new mutants with defects in distinct parts of the facial skeleton. In one mutant, which is defective for an Integrin protein that promotes cell adhesion, both a specific part of a cartilage element and the first “endodermal pouch” are missing. Pouches are extensions of the gut tube that will eventually fuse with the skin and form the gill slits of fish. By studying the integrina5 and other mutants, we are finding that the head endoderm has an early function in instructing neighboring crest cells to form region-specific skeletal shapes.

Another important question is how crest cells interpret signals from the endoderm to make skeletal elements of appropriate shapes. Hox proteins control skeletal shapes along the anterior-posterior axis. Normally, second arch crest cells have Hox proteins and make jaw-support cartilages, whereas more anterior first arch crest cells lack Hox proteins and make jaw cartilages instead. However, when Hox proteins are not made in the second arch, for example in moz and doublechin mutants, a duplicated jaw skeleton forms in place of the normal support skeleton. We have found that Hox genes specify the support skeleton by instructing second arch crest cells to respond to pouch endoderm signals. In another mutant, pucker, the dorsal skeleton is transformed to a ventral character and this correlates with an expansion of ventral dlx genes into the dorsal domain. Using these mutants, we hope to understand how anterior-posterior and dorsal-ventral identities are established, and consequently how these identities allow cells in distinct arch regions to respond to specific endoderm-derived signals and make unique skeletal shapes.

Patterson, M., Barske, L., Van Handel, B., Rau, C.D., Gan, P., Sharma, A., Parikh, S., Denholtz, M., Huang, Y., Yamaguchi, Y., Shen, H., Allayee, H., Crump, J.G., Force, T.I., Lien, C.L., Makita, T., Lusis, A.J., Kumar, S.R., Sucov, H.M. (2017) Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nature Genetics. 49(9):1346-1353
Askary, A., Xu, P., Barske, L., Bay, M., Bump, P., Balczerski, B., Bonaguidi, M.A., Crump, J.G. (2017) Genome-wide analysis of facial skeletal regionalization in zebrafish. Development (Cambridge, England). 144(16):2994-3005
Teng, C.S., Yen, H.Y., Barske, L., Smith, B., Llamas, J., Segil, N., Go, J., Sanchez-Lara, P.A., Maxson, R.E., Crump, J.G. (2017) Requirement for Jagged1-Notch2 signaling in patterning the bones of the mouse and human middle ear. Scientific Reports. 7:2497
Smeeton, J., Askary, A., Crump, J. G. (2017) Building and maintaining joints by exquisite local control of cell fate. Wiley interdisciplinary reviews. Developmental biology. 6(1)
Paul, S., Crump, J.G. (2016) Lessons on skeletal cell plasticity from studying jawbone regeneration in zebrafish. Bonekey Reports. 5:853
Askary, A., Smeeton, J., Paul, S., Schindler, S., Braasch, I., Ellis, N.A., Postlethwait, J., Miller, C.T., Crump, J.G. (2016) Ancient origin of lubricated joints in bony vertebrates. eLIFE. 5
Paul, S., Schindler, S., Giovannone, D., de Millo Terrazzani, A., Mariani, F.V., Crump, J.G. (2016) Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration. Development (Cambridge, England). 143(12):2066-76
Barske, L., Askary, A., Zuniga, E., Balczerski, B., Bump, P., Nichols, J.T., Crump, J.G. (2016) Competition between Jagged-Notch and Endothelin1 Signaling Selectively Restricts Cartilage Formation in the Zebrafish Upper Face. PLoS Genetics. 12:e1005967
Askary, A., Mork, L., Paul, S., He, X., Izuhara, A.K., Gopalakrishnan, S., Ichida, J.K., McMahon, A.P., Dabizljevic, S., Dale, R., Mariani, F.V., Crump, J.G. (2015) Iroquois Proteins Promote Skeletal Joint Formation by Maintaining Chondrocytes in an Immature State. Developmental Cell. 35:358-65
Choe, C.P., Crump, J.G. (2015) Eph-Pak2a signaling regulates branching of the pharyngeal endoderm by inhibiting late-stage epithelial dynamics. Development (Cambridge, England). 142(6):1089-94
Mork, L., Crump, G. (2015) Zebrafish Craniofacial Development: A Window into Early Patterning. Current topics in developmental biology. 115:235-69
Kim, A.D., Melick, C.H., Clements, W.K., Stachura, D.L., Distel, M., Panáková, D., MacRae, C., Mork, L.A., Crump, J.G., Traver, D. (2014) Discrete Notch signaling requirements in the specification of hematopoietic stem cells. The EMBO journal. 33(20):2363-73
Choe, C.P., Crump, J.G. (2014) Tbx1 controls the morphogenesis of pharyngeal pouch epithelia through mesodermal Wnt11r and Fgf8a. Development (Cambridge, England). 141(18):3583-93
Choe, C.P., Collazo, A., Trinh, L.A., Pan, L., Moens, C.B., and Crump, J.G. (2013) Wnt-Dependent Epithelial Transitions Drive Pharyngeal Pouch Formation. Developmental Cell. 24(3):296-309
Heur, M., Jiao, S., Schindler, S., and Crump, J.G. (2013) Regenerative potential of the zebrafish corneal endothelium. Experimental Eye Research. 106:1-4
Medeiros, D.M., and Crump, J.G. (2012) New perspectives on pharyngeal dorsoventral patterning in development and evolution of the vertebrate jaw. Developmental Biology. 371(2):121-135
Cox, S.G., Kim, H., Garnett, A.T., Medeiros, D.M., An, W., and Crump, J.G. (2012) An essential role of variant histone h3.3 for ectomesenchyme potential of the cranial neural crest. PLoS Genetics. 8(9):e1002938
Witzel, H.R., Jungblut, B., Choe, C.P., Crump, J.G., Braun, T., and Dobreva, G. (2012) The LIM Protein Ajuba Restricts the Second Heart Field Progenitor Pool by Regulating Isl1 Activity. Developmental Cell. 23(1):58-70
Balczerski, B., Matsutani, M., Castillo, P., Osborne, N., Stainier, D.Y., and Crump, J.G. (2012) Analysis of Sphingosine-1-phosphate signaling mutants reveals endodermal requirements for the growth but not dorsoventral patterning of jaw skeletal precursors. Developmental Biology. 361(2):230-241
Das, A., and Crump, J.G. (2012) Bmps and id2a act upstream of twist1 to restrict ectomesenchyme potential of the cranial neural crest. PLoS Genetics. 8(5):e1002710
Zuniga, E., Rippen, M., Alexander, C., Schilling, T.F., and Crump, J.G. (2011) Gremlin 2 regulates distinct roles of BMP and Endothelin 1 signaling in dorsoventral patterning of the facial skeleton. Development (Cambridge, England). 138(23):5147-5156
Alexander, C., Zuniga, E., Blitz, I.L., Wada, N., Le Pabic, P., Javidan, Y., Zhang, T., Cho, K.W., Crump, J.G., and Schilling, T.F. (2011) Combinatorial roles for BMPs and Endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton. Development (Cambridge, England). 138(23):5135-5146
Lou, X., Deshwar, A.R., Crump, J.G., and Scott, I.C. (2011) Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo. Development (Cambridge, England). 138(15):3113-23
Yamamoto, M., Morita, R., Mizoguchi, T., Matsuo, H., Isoda, M., Ishitani, T., Chitnis, A.B., Matsumoto, K., Crump, J.G., Hozumi, K., Yonemura, S., Kawakami, K., and Itoh, M. (2010) Mib-Jag1-Notch signalling regulates patterning and structural roles of the notochord by controlling cell-fate decisions. Development (Cambridge, England). 137(15):2527-2537
Zuniga, E., Stellabotte, F., and Crump, J.G. (2010) Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face. Development (Cambridge, England). 137(11):1843-1852
Laue, K., Daujat, S., Crump, J.G., Plaster, N., Roehl, H.H., Tübingen 2000 Screen Consortium, Kimmel, C.B., Schneider, R., and Hammerschmidt, M. (2008) The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity. Development (Cambridge, England). 135(11):1935-1946
Crump, J.G., Swartz, M.E., Eberhart, J.K., and Kimmel, C.B. (2006) Moz-dependent Hox expression controls segment-specific fate maps of skeletal precursors in the face. Development (Cambridge, England). 133(14):2661-9
Eberhart, J.K., Swartz, M.E., Crump, J.G., and Kimmel, C.B. (2006) Early Hedgehog signaling from neural to oral epithelium organizes anterior craniofacial development. Development (Cambridge, England). 133(6):1069-1077
Yan, Y.L., Willoughby, J., Liu, D., Crump, J.G., Wilson, C., Miller, C.T., Singer, A., Kimmel, C., Westerfield, M., and Postlethwait, J.H. (2005) A pair of Sox: distinct and overlapping functions of zebrafish sox9 co-orthologs in craniofacial and pectoral fin development. Development (Cambridge, England). 132(5):1069-1083
Crump, J.G., Maves, L., Lawson, N.D., Weinstein, B.M., and Kimmel, C.B. (2004) An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning. Development (Cambridge, England). 131(22):5703-5716
Crump, J.G., Swartz, M.E., and Kimmel, C.B. (2004) An Integrin-Dependent Role of Pouch Endoderm in Hyoid Cartilage Development. PLoS Biology. 2(9):E244
Kimmel, C.B., Ullmann, B., Walker, M., Miller, C.T., and Crump, J.G. (2003) Endothelin 1-mediated regulation of pharyngeal bone development in zebrafish. Development (Cambridge, England). 130(7):1339-1351

Patel, M.R., Lehrman, E.K., Poon, V.Y., Crump, J.G., Zhen, M., Bargmann, C.I., and Shen, K. (2006). Hierarchical assembly of presynaptic components in defined C. elegans synapses. Nat Neurosci 9(12),1488-98

Kishi, M., Pan, Y.A., Crump, J.G., and Sanes J.R. (2005). Mammalian SAD Kinases Are Required for Neuronal Polarization. Science 307, 929-932.

Dwyer, N.D., Adler, C.E., Crump, J.G., L'Etoile, N.D., and C.I. Bargmann (2001). Polarized Dendritic Transport and the AP-1 mu1 Clathrin Adaptor UNC-101 Localize Odorant Receptors to Olfactory Cilia. Neuron 31, 277-287.

Crump, J.G., Zhen, M., Jin, Y., and C.I. Bargmann (2001). The SAD-1 Kinase Regulates Presynaptic Vesicle Clustering and Axon Termination. Neuron 29, 115-129.

Roayaie, K.*, Crump, J.G.*, Sagasti, A., and C.I. Bargmann (1998). The G alpha Protein ODR-3 Mediates Olfactory and Nociceptive Function and Controls Cilium Morphogenesis in C. elegans Olfactory Neurons. Neuron 20, 55-67. (*these authors contributed similarly to this work)

Chou, J.H., Troemel, E.R., Sengupta, P., Colbert, H.A., Tong, L., Tobin, D.M., Koayaie, K., Crump, J.G., Dwyer, N.D., and C.I. Bargmann (1996). Olfactory Recognition and Discrimination in Caenorhabditis elegans. Cold Spring Harbor Symposia on Quantitative Biology, Volume LXI, 157-164.