Thomas Schilling, Ph.D.
Zebrafish developmental genetics – Our laboratory uses genetics and molecular biology to study pattern formation in the early zebrafish embryo. The rapid development and simple anatomy of this teleost embryo, together with recently developed techniques for reverse genetics and a nearly complete genome sequence, make zebrafish a powerful molecular genetic system for studying the mechanisms of development. We focus on two areas: (i) neural crest specification and formation of the skeleton in the early embryo and (ii) long-range signals, morphogens, that pattern the anterior-posterior (A-P) axis of the nervous system. In both cases, we are interested in how gene functions translate into cell behaviours and the formation of tissues and organs.
A major focus of the work in our laboratory is to define as fully as possible the genetic and molecular pathways that establish the neural crest and its derivatives. Neural crest is a population of highly migratory cells that arise from the crests of the forming neural tube as it folds, and give rise to all of the body’s pigmentation, most of its peripheral nervous system, as well as the head skeleton. We have been analyzing and cloning the genes underlying a large library of mutations identified by their defects in the craniofacial skeleton. We have also identified downstream targets that we now believe control neural crest migration, and these share many similarities with other migrating cell types, such as metastatic cancer cells.
A second focus of our lab is to understand the genetic and molecular pathways that specify the identities of cells along the A-P axis in the early embryo, including neural crest. Here we have begun to take a more computational, systems approach. The vitamin A derivative, retinoic acid (RA), is thought to be a diffusible factor that promotes posterior development. Zebrafish mutants in an enzyme that synthesizes RA, called Retinaldehyde dehydrogenase (Raldh2), have defects in the formation of segments in the hindbrain, known as rhombomeres, that each contain unique sets of interneurons and motor neurons. More recently, my lab has studied requirements for: 1) other Raldh enzymes, 2) RA receptors (RARs), 3) cellular RA binding proteins (CRABPs), and 4) RA degrading enzymes (Cyp26s), in signaling.
- Wang K, Vorontsova I, Hoshino M, Uesugi K, Yagi N, Hall JE, Schilling TF and Pierscionek BK (2021). Aquaporins have regional functions in development of refractive index in the zebrafish eye lens. Investigative Opthalmology and Visual Science March 2021 doi:https://doi.org/10.1167/iovs.62.3.23.
- Heubel B, Bredesen C, Schilling TF and LePabic P (2020). Endochondral growth zone pattern and activity in the zebrafish pharyngeal skeleton. Developmental Dynamics 2020 Aug 27 doi:10.1002/dvdy.241.
- Niu X, Subramanian A, Hwang TH, Schilling TF and Galloway JL (2020). Tendon cell regeneration is mediated by attachment-site resident progenitors and BMP signaling. Current Biology 2020 Jun 29:S0960-9822(20)30832-0. doi: 10.1016/j.cub.2020.06.016
- Wang K, Vorontsova I, Hoshino M, Uesugi K, Yagi N, Hall JE, Schilling TF and Pierscionek BK (2020). Optical development in the zebrafish eye lens. FASEB Journal doi.org/10.1096/fj.201902607R
- Hendrick L, Carter GA, Hilbrands EH, Heubel BP, Schilling TF and Le Pabic P (2019). Tracking pigment progenitors reveals distinct modes of bar, stripe and spot development in sand-dweller cichlids from Lake Malawi. EvoDevo 2019 Aug 12;10:18. doi: 10.1186/s1186/s13227-019-0132-7.
- Vorontsova I, Hall J and Schilling TF (2019). Assessment of zebrafish lens nucleus localization and sutural integrity. Journal of Visualized Experiments (JoVE) May 6;(147). doi:10.3791/59528.
- Sharma P, MacLean A, Clouthier D, Nie Q and Schilling TF (2019). Transcriptomics reveals complex kinetics of dorsal-ventral patterning gene expression in the mandibular arch. Genesis 2018 Dec 18:e23275. doi:10/1002/dvg.23275.
- Subramanian A, Kanzaki L, Galloway JL and Schilling TF (2018). Mechanical force regulates tendon extracellular matrix organization and tenocyte morphogenesis through TGFbeta signaling. eLife 2018;7. E38069. doi: 10.7554/eLife.38069.
- Meinecke L*, Sharma P*, Du H, Zhang L, Nie Q# and Schilling TF# (2018). Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch. PLoS Computational Biology 14(11):e1006569. doi: 10.1371/journal.pcbi.1006569. (*co-first authors; # – co-senior authors)
- Vorontzova I, Gehring I, Hall JE, and Schilling TF (2018). Aquaporin-0 regulates suture stability in the zebrafish lens. Investigative Ophthalmology and Visual Science 59, 2869-2879. doi:10.1116/iovs.18-24044.
- Rackaukas C, Schilling TF and Nie Q (2018). Mean-independent noise attenuation via intermediate states. iScience 3, 11-20. https:oi.org/10.1016/j.isci.2018.04.002.
- Aguillon R, Batut J, Subramanian A, Madelaine R, Dufourcq P, Schilling TF and Blader P (2018). Cell-type heterogeneity in the zebrafish olfactory placode is generated from progenitors within the preplacodal ectoderm. eLife 2018;7:e32041: doi: https://doi.org/org/10.7554/eLife.32041.
- Wang W, Holmes WR, Sosnik J, Schilling TF and Nie Q (2017). Cell sorting and noise-induced plasticity coordinate to sharpen boundaries between gene expression domains. PLoS Computational Biology 13(1):e1005307. doi: 10.1371/journal.pcbi.1005307.
- Muto A and Schilling TF (2017). Zebrafish as a model to study cohesin and cohesinopathies. In K Yokomori and Katsuhiko Shirahige (Eds.). Cohesin and Condensin: Methods and Protocols. Methods in Mol Biol. Vol 1515, pp. 177-196 Springer Press.
- Vibert L, Aquino G, Gehring I, Subkhankulova T, Schilling TF, Rocco A and Kelsh RN (2016). An ongoing role for Wnt signaling in differentiating melanocytes in vivo. Pigment Cell Melanoma Research doi: 10.1111/pcmr.12568.
- Nichols J, Dowd J, Watson S, Parthasarathy R, Brooks E, Subramanian A, Nachtrab G, Poss KD, Schilling TF, and Kimmel CB. (2016). Repetitive element silencing buffers a mef2ca dependent ligament versus bone fate decision in the zebrafish craniofacial skeleton. Development 143, 4430-4440.
- Schilling TF, Sosnik J and Q Nie (2016). Visualizing retinoic acid morphogen gradients. In HW Detrich III, M Westerfield and LI Zon (Eds.). The Zebrafish: Cellular and Developmental Biology, Part A Cellular Biology (pp. 139-163). Methods in Cell Biol Vol 133. Elsevier Inc., Academic Press.
- Kawauchi S, Santos R, Muto A, Lopez-Burks M, Schilling TF, Lander AD and Calof AL (2016). Using vertebrate animal models to understand the etiology of developmental defects in Cornelia de Lange Syndrome. Am J Hum Genet C Semin Med Genet doi:10.1002/ajmg.c.31484.
- Sosnik J, Zheng L, Rackauckas CV, Gratton E, Nie Q, and Schilling TF. (2016). Noise modulation of retinoic acid signaling controls sharpening of segmental gene expression boundaries in the zebrafish hindbrain. eLife 5:e14034. doi:10.7554/eLife.14034.
- Le Pabic P, Cooper J and Schilling TF (2016). Developmental basis of phenotypic integration in two Lake Malawi cichlids. EvoDevo 21 7:3 doi: 10.1186/s13227-016-0040-z.
- Subramanian A, and Schilling TF (2015). Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix. Development 142, 4191-4204. doi: 10.1242/dev.114777.
- Cruz IA, Kappedal R, Mackenzie S, Hoffman TL, Schilling TF and Raible DW (2015). Robust regeneration of adult zebrafish lateral line hair cells reflects continued precursor pool maintenance. Developmental Biology 402, 229-238. doi: 10.1016/j.ydbio.2015.03.019.
- Boer, EF, Howell, ED, Schilling, TF, Jette, CA and Stewart RA (2015). Fascin1-dependent filopodia are required for directional migration of a subset of neural crest cells. PLoS Genetics 11(1):e1004946. doi: 10.1371/journal.pgen.1004946.
- Le Pabic P, Ng C and Schilling TF (2014). Fat-Dachsous signaling coordinates cartilage differentiation and polarity during craniofacial development. PLoS Genetics 10(10):e1004726. doi: 10.1371/journal.pgen.1004726.
- Muto A, Ikeda S, Lopez-Burks ME, Kikuchi Y, Calof AL, Lander AD and Schilling TF (2014). Nipbl and Mediator cooperatively regulate gene expression to control limb development. PLoS Genetics 10(9):e1004671. doi: 10.1371/journal.pgen.1004671.
- Alexander C, Piloto S, Le Pabic P and Schilling TF (2014). Wnt signaling interacts with Bmp and Edn1 to regulate dorsal-ventral patterning and growth of the craniofacial skeleton. PLoS Genetics 10(7):e1004479. doi: 10.1371/journal.pgen.1004479.
- Subramanian A and Schilling TF (2014). Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions. eLife (Cambridge) doi: 10.7554/eLife.02372.
- Tuttle A, Hoffman T and Schilling TF (2014). rabconnectin-3a regulates vesicle endocytosis and canonical Wnt signaling in zebrafish neural crest migration. PLoS Biology 12(5): e1001852. doi:10.1371/journal.pbio.1001852. Article recommended in Faculty of 1000.
- Schilling TF and Le Pabic P (2014). Neural crest cells in craniofacial skeletal development. In Neural Crest Cell Differentiation and Disease (ed. P Trainor). (pp. 127-151). Elsevier.