Associate Professor, Department of Developmental & Molecular Biology
Associate Professor, Dominick P. Purpura Department of Neuroscience
Every animal starts out as a single fertilized cell, yet we do not fully understand the events that are essential for producing that cell because they take place within the ovary of the mother. Failure to form an egg that is capable of embryonic development can result in profound birth defects or miscarriage. In addition, cancers of the ovary can arise from uncontrolled proliferation of the germ cells, those cells that can become eggs, or the somatic cells, the cells that do not develop as eggs, of the ovary. In normal ovaries, these two types of cells communicate with one another to regulate the growth and survival of both cell populations. In most animals, the germ line stem cells undergo an asymmetric division to generate daughter cells that will remain stem cells and others, cystoblasts that divide and eventually form eggs. The divisions of the cystoblasts are unique because the cells do not completely separate from one another, but instead remain attached to each other. Studies in mammals show that the connections between cystoblasts prevent too many cells from becoming oocytes, and in humans uncontrolled and complete separation of cystoblasts correlates with germ cell neoplasias. However, since these events occur before or at the time of fertilization we understand little about how the genes that are involved. Therefore, understanding how the growth and survival of these cells is regulated has important consequences to both fertility and cancer formation.
To study relationships between interacting cells within adjacent tissues, such as germline and somatic follicle cells, we need to analyze an animal system in which we can manipulate genes and study early development. The zebrafish system has advantages that allow us to use embryological, biochemical, and genetic techniques to access maternally controlled processes during vertebrate animal development. Our studies exploit the powerful genetics and cell biological access in the zebrafish system to unravel the mechanisms that regulate oocyte polarization and follicle cell fate in a vertebrate. Several features of primary oocyte development are common among insects, and vertebrates, including humans, thus this architecture is likely fundamental for germline development and fertility.
Our genetic and biochemical studies of oocyte polarity have led us to genes involved in mRNA localization and polarized transport, including motor and RNA binding proteins. Like oocytes, neurons are highly polarized cells, which rely on trafficking and post-transcriptional regulation of mRNAs to ensure that gene products are only expressed in discrete locations. Inappropriate accumulation of proteins and organelles due to failed trafficking and post-transcriptional regulation is associated with neuronal loss underlying devastating neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s, Parkinson’s and Huntington’s disease. The rapid development, optical clarity, and ease of generating transgenic and mutant zebrafish strains make it an ideal system for live cell tracking and visualization of fluorescently labeled organelles, motor proteins, mRNA cargos, and the cytoskeleton in the living animal. To better understand how trafficking is regulated in distinct polarized cell types, we are also using the zebrafish model system to examine the cellular and molecular basis of transport in neurons. Knowledge of how the individual transport mechanisms operating in neurons contribute to their function has potential to uncover novel pathological mechanisms underlying neurodegenerative diseases.
Zaucker A, Mercurio S, Sternheim N, Talbot WS, Marlow FL. notch3 is essential for oligodendrocyte development and vascular integrity in zebrafish. Disease Models and Mechanisms. Epub: 2013 May 29. In press.
Campbell, PD, Marlow FL, Analysis of zebrafish kinesin-1 kif5 heavy chain genes during zebrafish development. Gene Expression Patterns. Epub 2013 May 15. 2013 Oct;13(7):271-9. doi: 10.1016/j.gep.2013.05.002.
Li X, Roszko I, Sepich DS, Ni M, Hamm H, Marlow FL*, Solnica-Krezel L.* The adhesion GPCR Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development. 2013 Jul;140(14):3028-39. doi: 10.1242/dev.094839. PMID: 23821037 *cocorresponding authors.
Nair S, Marlow FL, Abrams E, Kapp L, Mullins MC, Pelegri F. The Chromosomal Passenger Protein Birc5b Organizes Microfilaments and Germ Plasm in the Zebrafish Embryo. PLoS Genet. 2013 April; 9(4): e1003448. Published online 2013 April 18. doi: 10.1371/journal.pgen.1003448PMCID: PMC3630083.
Santos-Ledo A, Jenny A, Marlow FL. Comparative gene expression analysis of the fmnl family of formins during zebrafish embryogenesis and implications for tissue specific functions. Gene Expression Patterns. Epub: 2012 Oct 13. 2013 Jan-Feb;13(1-2):30-7. doi: 10.1016/j.gep.2012.09.002.
Besanceney C, Jiang H, Zheng T, Feng L, Soriano Del Amo D, Wang W, Klivansky L, Liu Y, Marlow F, Wu P. Raising the Efficacy of Bioorthogonal Click Reactions for Bioconjugation: A Comparative Study. Angew Chem Int Ed Engl. 2011 Jul 14. doi: 10.1002/anie.201101817. [Epub ahead of print]. PMID: 21761519.
Jiang H, Feng L,Soriano del Amo D, Marlow FL, and Wu P. Imaging glycans in zebrafish embryos by metabolic labeling and bioorthogonal click chemistry. J Vis Exp. 2011 Jun 6;(52). pii: 2686. doi: 10.3791/2686. PMID: 21673647.
Zheng T, Jiang H, Gros M, Soriano del Amo D, Sundaram S, Lauvau G, Marlow FL, StanleyP, and Wu P. Tracking of N-acetyllactosamine-bearing glycans on the cell surface in vivo. Angewandte Chemie. 2011; March.DOI: 10.1002/anie.201100265. PMID: 21472942.
Marlow FL. My Mother Made Me Do It! Maternal Control of Development in Vertebrates. Edited by Daniel Kessler. Morgan and Claypool. Colloquium Series on Developmental Biology, 2010, Vol. 1, No. 1, Pages 1-217 (doi: 10.4199/C00023ED1V01Y201012DEB005).
Soriano del Amo D, Wang W, Jiang H, Besanceney C, Yan A, Levy M, Liu Y, Marlow FL and Wu P. Dynamic in vivo imaging using biocompatible copper(I) catalysts. JACs. 2010 Nov; 132: 16893.
Gupta T, Marlow FL, Ferriola D, Mackiewicz K, Dapprich J, Monos D, Mullins MC. Microtubule Actin Crosslinking Factor 1 Regulates Balbiani Body Function and Animal-Vegetal Polarity of the Zebrafish Oocyte. PLOS Genetics. 2010.
Nojima H, Röthhämel S, Shimizu T, Kim C, Yonemura S, Marlow FL & Hibi M. Syntabulin, a linker of the motor protein, controls dorsal determination in zebrafish embryos. Development. 2010; Feb; 137: 923-933.
Mei W, Lee KW, Marlow FL, Miller AL, and Mullins MC. hnRNP I/brom bones is required for Ca2+-mediated egg activation in the zebrafish. Development. 2009 Sept;136 (17):3007-17.
Bontems F*, Stein A*, Marlow F*, Lyautey J, Gupta T, Mullins MC and Dosch R. Bucky ball organizes germ plasm assembly in the zebrafish oocyte. Current Biology. 2009. Feb 25; 19: 414-422 *Co-first authors.
Alvarez-Delfin, K, Morris AC, Snelson C, Burgess H, Gupta T, Marlow F, Gamse JT, Mullins, MC, and Fadool JM. tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development. Proc Natl Acad Sci U S A. 2009 Feb 10; 106 (6): 2023-8.
Marlow FL and Mullins MC. Bucky ball functions in Balbiani body assembly and animal-vegetal polarity in the oocyte and follicle cell layer in zebrafish. Dev. Bio. Published online June 9 2008.
Blaser H., Reichman-Fried M, Castanon I, Dumstrei K, Marlow FL, Kawakami K, Solnica-Krezel L, Heisenberg C-P and Raz E. Migration of Zebrafish Primordial Germ Cells: a Role for Myosin Contraction and Cytoplasmic Flow. Developmental Cell 2006 Nov 11; (5): 613-27.
Marlow F*, Gonzalez EM*, Yin C, Rojo C, and Solnica Krezel L. No tail cooperates with non-canonical Wnt signaling to regulate posterior body morphogenesis in zebrafish. Development 2003 Dec 3; (131): 203-216.
Jessen JR, Topczewski J, Bingham S, Sepich DS, Marlow F, Chandrasekhar A, Solnica-Krezel L. Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. Nat Cell Biol. 2002 Aug 4; (8): 610-5.
Marlow F, Topczewski J, Sepich D, Solnica-Krezel L. Zebrafish Rho Kinase 2 Acts Downstream of Wnt11 to Mediate Cell Polarity and Effective Convergence and Extension Movements. Current Biology 2002 Jun 4; 12(11): 876-84.
Sepich DS, Myers DC, Short R, Topczewski J, Marlow F, Solnica-Krezel L. Role of the Zebrafish trilobite Locus in Gastrulation Movments of Convergence and Extension. Genesis 2000 Aug 27; (4): 159-173.
Marlow F, Zwartkruis F, Malicki J, Neuhauss SC, Abbas L, Weaver M, Driever W, Solnica-Krezel L. Functional interactions of genes mediating convergent extension, knypek and trilobite, during the partitioning of the eye primordium in zebrafish. Developmental Biology 1998 Nov 15; 203(2): 382-99.
More Information About Dr. Florence Marlow
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Chanin Building, Room 514
Bronx, NY 10461