Alvaro Sagasti
Professor, Molecular, Cell and Developmental Biology, University of California Los Angeles
Mailing Address:
P.O. Box 951606
Los Angeles, CA 90095
Office Address:
BSRB 450B
621 Charles E. Young Dr. S
Los Angeles, CA 90069
Fax Number:
310-206-3987
Affiliations
Member, Brain Research Institute, Cell & Developmental Biology GPB Home Area, Neuroscience GPB Home Area
Research Interests
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.
Biography
Dr. Sagasti received his PhD from UCSF, where he worked with Cori Bargmann studying celll specification and left/right asymmetry in the nervous system of the nematode C. elegans. He began using zebrafish as a model at the Skirball Institute, NYU Medical Center as a post-doc with Alex Schier. In the summer of 2005 he was a Grass Foundation Fellow at the Marine Biological Labs in Woods Hole, Massachussetts. He began as a UCLA faculty member in the MCDB department in September 2005. His lab uses a combination of imaging, molecular, and genetic approaches in zebrafish to investigate on the morphogenesis of sensory axons and skin cells during development and repair.
Awards and Honors
- Distinguished Teaching Award, UCLA, 2017.
- Life Sciences Excellence Award in Educational Innovation, UCLA, 2022.
Publications
- Peterman E, Quitevis EJA, Black EC, Horton EC, Aelmore RL, White E, Sagasti A, Rasmussen JP. Zebrafish cutaneous injury models reveal Langerhans cells engulf axonal debris in adult epidermis.. Disease models & mechanisms, 2023.
- Adula KP, Sagasti A. Live Imaging of Axonal Dynamics After Laser Axotomy of Peripheral Neurons in Zebrafish.. Methods in molecular biology (Clifton, N.J.), 2023.
- Rosa JB, Nassman KY, Sagasti A. Sensory axons induce epithelial lipid microdomain remodeling and determine the distribution of junctions in the epidermis.. Molecular biology of the cell, 2022.
- Adula KP, Shorey M, Chauhan V, Nassman K, Chen SF, Rolls MM, Sagasti A. The MAP3Ks DLK and LZK Direct Diverse Responses to Axon Damage in Zebrafish Peripheral Neurons.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022.
- Lu TQ, van Loon AP, Sagasti A. How to wrinkle a cell: Emerging mechanisms of microridge morphogenesis.. Current opinion in cell biology, 2022.
- Shorey M, Rao K, Stone MC, Mattie FJ, Sagasti A, Rolls MM. Microtubule organization of vertebrate sensory neurons in vivo.. Developmental biology, 2021.
- van Loon AP, Erofeev IS, Goryachev AB, Sagasti A. Stochastic contraction of myosin minifilaments drives evolution of microridge protrusion patterns in epithelial cells.. Molecular biology of the cell, 2021.
- Inaba Y, Chauhan V, van Loon AP, Choudhury LS, Sagasti A. Keratins and the plakin family cytolinker proteins control the length of epithelial microridge protrusions.. eLife, 2020.
- van Loon AP, Erofeev IS, Maryshev IV, Goryachev AB, Sagasti A. Cortical contraction drives the 3D patterning of epithelial cell surfaces.. The Journal of cell biology, 2020.
- Cokus SJ, De La Torre M, Medina EF, Rasmussen JP, Ramirez-Gutierrez J, Sagasti A, Wang F. Tissue-Specific Transcriptomes Reveal Gene Expression Trajectories in Two Maturing Skin Epithelial Layers in Zebrafish Embryos.. G3 (Bethesda, Md.), 2019.
- Feng C, Thyagarajan P, Shorey M, Seebold DY, Weiner AT, Albertson RM, Rao KS, Sagasti A, Goetschius DJ, Rolls MM. Patronin-mediated minus end growth is required for dendritic microtubule polarity.. The Journal of cell biology, 2019.
- Rosa JB, Sagasti A. Developmental Neurobiology: It Takes Nrg to�Separate�Dendrites.. Current biology : CB, 2019.
- Jiang N, Rasmussen JP, Clanton JA, Rosenberg MF, Luedke KP, Cronan MR, Parker ED, Kim HJ, Vaughan JC, Sagasti A, Parrish JZ. A conserved morphogenetic mechanism for epidermal ensheathment of nociceptive sensory neurites.. eLife, 2019.
- Julien DP, Chan AW, Barrios J, Mathiaparanam J, Douglass A, Wolman MA, Sagasti A. Zebrafish expression reporters and mutants reveal that the IgSF cell adhesion molecule Dscamb is required for feeding and survival.. Journal of neurogenetics, 2018.
- Rasmussen JP, Vo NT, Sagasti A. Fish Scales Dictate the Pattern of Adult Skin Innervation and Vascularization.. Developmental cell, 2018.
- Madigan CA, Cambier CJ, Kelly-Scumpia KM, Scumpia PO, Cheng TY, Zailaa J, Bloom BR, Moody DB, Smale ST, Sagasti A, Modlin RL, Ramakrishnan L. A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.. Cell, 2017.
- Lulla A, Barnhill L, Bitan G, Ivanova MI, Nguyen B, O'Donnell K, Stahl MC, Yamashiro C, Klärner FG, Schrader T, Sagasti A, Bronstein JM. Neurotoxicity of the Parkinson Disease-Associated Pesticide Ziram Is Synuclein-Dependent in Zebrafish Embryos.. Environmental health perspectives, 2016.
- Rasmussen JP, Sagasti A. Learning to swim, again: Axon regeneration in fish.. Experimental neurology, 2016.
- Vargas ME, Yamagishi Y, Tessier-Lavigne M, Sagasti A. Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015.
- Rasmussen JP, Sack GS, Martin SM, Sagasti A. Vertebrate epidermal cells are broad-specificity phagocytes that clear sensory axon debris.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015.
- Julien DP, Sagasti A. Synaptic specificity: when the neighbors are away, sensory axons turn promiscuous.. Current biology : CB, 2014.
- Chun RF, Blatter E, Elliott S, Fitz-Gibbon S, Rieger S, Sagasti A, Adams JS, Hewison M. Cloning of a functional 25-hydroxyvitamin D-1a-hydroxylase in zebrafish (Danio rerio).. Cell biochemistry and function, 2014.
- O'Donnell KC, Lulla A, Stahl MC, Wheat ND, Bronstein JM, Sagasti A. Axon degeneration and PGC-1a-mediated protection in a zebrafish model of a-synuclein toxicity.. Disease models & mechanisms, 2014.
- O'Donnell KC, Vargas ME, Sagasti A. WldS and PGC-1a regulate mitochondrial transport and oxidation state after axonal injury.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013.
- Wang F, Julien DP, Sagasti A. Journey to the skin: Somatosensory peripheral axon guidance and morphogenesis.. Cell adhesion & migration, 2013.
- Palanca AM, Sagasti A. Optogenetic activation of zebrafish somatosensory neurons using ChEF-tdTomato.. Journal of visualized experiments : JoVE, 2013.
- Fitzmaurice AG, Rhodes SL, Lulla A, Murphy NP, Lam HA, O'Donnell KC, Barnhill L, Casida JE, Cockburn M, Sagasti A, Stahl MC, Maidment NT, Ritz B, Bronstein JM. Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease.. Proceedings of the National Academy of Sciences of the United States of America, 2012.
- Palanca AM, Lee SL, Yee LE, Joe-Wong C, Trinh le A, Hiroyasu E, Husain M, Fraser SE, Pellegrini M, Sagasti A. New transgenic reporters identify somatosensory neuron subtypes in larval zebrafish.. Developmental neurobiology, 2012.
- Issa FA, Mock AF, Sagasti A, Papazian DM. Spinocerebellar ataxia type 13 mutation that is associated with disease onset in infancy disrupts axonal pathfinding during neuronal development.. Disease models & mechanisms, 2012.
- Villegas R, Martin SM, O'Donnell KC, Carrillo SA, Sagasti A, Allende ML. Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types.. Neural development, 2012.
- O'Brien GS, Rieger S, Wang F, Smolen GA, Gonzalez RE, Buchanan J, Sagasti A. Coordinate development of skin cells and cutaneous sensory axons in zebrafish.. The Journal of comparative neurology, 2012.
- Wang F, Wolfson SN, Gharib A, Sagasti A. LAR receptor tyrosine phosphatases and HSPGs guide peripheral sensory axons to the skin.. Current biology : CB, 2012.
- Rieger S, Sagasti A. Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin.. PLoS biology, 2011.
- Rieger S, Wang F, Sagasti A. Time-lapse imaging of neural development: zebrafish lead the way into the fourth dimension.. Genesis (New York, N.Y. : 2000), 2011.
- Issa FA, O'Brien G, Kettunen P, Sagasti A, Glanzman DL, Papazian DM. Neural circuit activity in freely behaving zebrafish (Danio rerio).. The Journal of experimental biology, 2011.
- Martin SM, O'Brien GS, Portera-Cailliau C, Sagasti A. Wallerian degeneration of zebrafish trigeminal axons in the skin is required for regeneration and developmental pruning.. Development (Cambridge, England), 2010.
- Grueber WB, Sagasti A. Self-avoidance and tiling: Mechanisms of dendrite and axon spacing.. Cold Spring Harbor perspectives in biology, 2010.
- O'Brien GS, Martin SM, S?llner C, Wright GJ, Becker CG, Portera-Cailliau C, Sagasti A. Developmentally regulated impediments to skin reinnervation by injured peripheral sensory axon terminals.. Current biology : CB, 2009.
- O'Brien GS, Sagasti A. Fragile axons forge the path to gene discovery: a MAP kinase pathway regulates axon regeneration.. Science signaling, 2009.
- O'Brien GS, Rieger S, Martin SM, Cavanaugh AM, Portera-Cailliau C, Sagasti A. Two-photon axotomy and time-lapse confocal imaging in live zebrafish embryos.. Journal of visualized experiments : JoVE, 2009.
- Richler E, Chaumont S, Shigetomi E, Sagasti A, Khakh BS. Tracking transmitter-gated P2X cation channel activation in vitro and in vivo.. Nature methods, 2007.
- Sagasti A. Three ways to make two sides: genetic models of asymmetric nervous system development.. Neuron, 2007.
- Merchant SS, Sagasti A. Precious metal economy.. Cell metabolism, 2006.
- Sagasti A, Guido MR, Raible DW, Schier AF. Repulsive interactions shape the morphologies and functional arrangement of zebrafish peripheral sensory arbors.. Current biology : CB, 2005.
- Tanaka-Hino M, Sagasti A, Hisamoto N, Kawasaki M, Nakano S, Ninomiya-Tsuji J, Bargmann CI, Matsumoto K. SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans.. EMBO reports, 2001.