Morphogenesis of sensory neurons and skin
Morphogenesis is the process by which cells adopt their specific shapes, sizes, and relationships with neighboring cells. Our lab studies the morphogenesis of developing skin cells and sensory neurons, which together mediate touch sensation. The skin at early developmental stages consists of two epithelial layers, each with distinct functions and morphologies. Sensory neurons project elaborately branched cellular processes called peripheral axons into the territory between the two skin layers to detect touch stimuli. We investigate how each of these cell types adopts its distinct morphological features and how skin cells and neurons influence each other?s morphogenesis.
To study these questions we use zebrafish embryos and larvae as a model. Because zebrafish eggs are externally fertilized and their embryos are optically clear, cellular behaviors can be imaged in live animals. Transgenic lines allow us to visualize specific cells and subcellular processes, laser-based techniques allow us to damage cells at precise times and places to study repair, and genetic manipulations provide insight into the molecular underpinnings of cellular behaviors. By studying basic cellular processes we hope to shed light on how they are impacted by damage and disease.
Julien, D.P., Chan, A.W., Barrios, J., Mathiaparanam, J., Douglass, A., Wolman, M. A. and A. Sagasti, "Zebrafish expression reporters and mutants reveal that the IgSF cell adhesion molecule Dscamb is required for feeding and survival", Journal of Neurogenetics 1-17 (2018).
Rasmussen, J.P., Vo, N-T, and A. Sagasti, "Fish scales dictate the pattern of adult skin innervation and vascularization", Developmental Cell 46 (3): 344-359 (2018).
Madigan, C.A., Cambier, C.J., Kelly-Scumpia, KM, Scumpia, P.O., Cheng, T.Y., Zailaa, J., Bloom, B.R., Moody, D.B., Smale, S.T., Sagasti, A., Modlin, R.L., and L. Ramakrishnan, "A macrophage response to mycobacterium leprae phenolic glycolipid initiates nerve damage in leprosy", Cell 170 (5): 973-985 (2017).
Rasmussen, J.P., and A. Sagasti, "Learning to swim, again: Axon regeneration in fish", Experimental Neurology 287 (3): 318-330 (2016).
Lulla, A., Barnhill, L., Bitan, G., Ivanova, M.I., Nguyen, B., O'Donnell, K., Stahl, M.C., Yamashiro, C., Klarner, F.G., Schrader, T., Sagasti, A., and J.M. Bronstein, "Neurotoxicity of the Parkinson's Disease-Associated Pesticide Ziram Is Synuclein-Dependent in Zebrafish Embryos", Environ Health Perspect 124 (11): 1766-1775 (2016).
Rasmussen, J.P., Sack, G.S., Martin, S.M., Sagasti, A., "Vertebrate epidermal cells are broad-specificity phagocytes that clear sensory axon debris", Journal of Neuroscience 3 (2): 559-570 (2015).
Julien, D.P., Sagasti, A., "Synaptic specificity: when the neighbors are away, sensory axons turn promiscuous", Current Biology 24 (24): 1168-1170 (2014).
Chun, R.F., Blatter, E., Elliott, S., Fitz-Gibbon, S., Rieger, S., Sagasti, A., Adams, J.S., Hewison, M., "Cloning of a functional 25-hydroxyvitamin D-1?-hydroxylase in zebrafish (Danio rerio)", Cell Biochemistry and Function 32 (8): 675-682 (2014).
O'Donnell, K.C., Vargas, M.E., and A. Sagasti, "WldS and PGC-1α Regulate Mitochondrial Transport and Oxidation State after Axonal Injury", Journal of Neuroscience 33 (37): 14778-14790 (2013).
Wang F, Julien DP, and A. Sagasti, "Journey to the skin: Somatosensory peripheral axon guidance and morphogenesis", Cell Adhesion and Migration 7 (4): 388-394 (2013).
Palanca, A.M.S., Lee, S.L., Yee, L.E., Joe-Wong, C., Trinh, L.A., Hiroyasu, E., Husain, M., Fraser, S.E., Pellegrini, M. and A. Sagasti, "New transgenic reporters identify somatosensory neuron subtypes in larval zebrafish", Developmental Neurobiology 73 (2): 152-167 (2013).
Palanca, A.M.S. and A. Sagasti, "Optogenetic activation of zebrafish somatosensory neurons using ChEF-tdTomato", Journal of Visualized Experiments 71: (2013).
Fitzmaurice, A.G., Rhodes, S.L., Lulla, A., Murphy, N.P., Lam, H.A., O'Donnell, K.C., Barnhill, L., Casida, J.E., Cockburn, M., Sagasti, A., Stahl, M.C., Maidment, N.T., Ritz, B., and J.M. Bronstein, "Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease", Proc Natl Acad Sci U S A 110 (2): 636-641 (2013).
Issa, F.A., Mock, A.F., Sagasti, A. and D.M. Papazian, "Spinocerebellar ataxia type 13 mutation associated with disease onset in innfancy disrupts axonal pathfinding during neuronal development", Disease Models and Mechanisms 5: 921-929 (2012).
Villegas, R., Martin, S.M., O?Donnell, K.C., Carillo, S.A., Sagasti, A., and Allende, M.L., "Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types", Neural Development 7 (1): (2012).