Polarity in the Zebrafish Ovary.
Cellular asymmetries are utilized to generate pattern or function within individual cells and or tissues. The ovary is composed of co-dependent and polarized cell populations: germline derived oocyte cells and the somatic follicle cells that surround and support developing oocytes. Both individual cell polarization and tissue polarity play prominent roles in the formation of an ovary with polarized oocytes and specialized follicle cell types that are essential for fertility. However, the mechanisms that generate polarized oocytes and somatic cell fates are not understood in vertebrates. Our lab employs a combination of forward and reverse genetics with molecular and cell biological approaches feasible in zebrafish, to identify the genetic pathways and cellular mechanisms that establish and regulate polarity in oocytes and their surrounding supportive somatic follicle cells.
Germline stem cell division produces self-renewing cells and cystocytes, the cells that develop as oocytes. Before differentiating, cystocytes divide with incomplete cytokinesis to produce a group of interconnected cells known as a germline cyst. These cells are interconnected by cytoplasmic bridges, or ring canals, which are conserved across phyla, including zebrafish and mammals. Primary oocytes share an evolutionarily conserved asymmetry, the Balbiani body. The formation of germline cysts and organelle asymmetries in primary oocytes from insects to mammals suggests that this architecture plays important roles in germline development. Despite its documentation for over 100 years, the genes that regulate Balbiani body formation and its developmental function are not understood even in insects. The zebrafish bucky ball mutation ablates the Balbiani body, disrupts oocyte asymmetries, and demonstrates that failure to produce a polarized oocyte results in failure to form the first axis of the prospective embryo. We are using the bucky ball gene as an entry point to identify and understand the molecular and cellular mechanisms underlying the fundamental and conserved formation of germline cysts with polarized primary oocytes.
Cell fates within the somatic follicular cell layer also display animal-vegetal polarity in zebrafish. The Animal Vegital oocyte axis is evident by the localization of mRNAs and proteins. Morphologically, this axis is apparent by the localization of the oocyte nucleus and a specialized follicle cell, the micropylar cell, to the animal-pole in wild type. In bucky ball mutants an excess number of somatic follicle cells develop as micropylar cells. This indicates that somatic cell fate and germ cell polarity are interdependent or that asymmetry is coordinated in each cell type. Localization of bucky ball transcripts specifically in the oocyte suggests that polarized cell fates within the follicular epithelium depend on oocyte polarity. Polarized or asymmetric cell fates within the follicle cell layer is not unique to zebrafish; in Drosophila and in the mouse distinct cell fates are present within the follicle cell layer at distinct positions relative to the oocyte position or oocyte axis. We are interested in identifying the mechanisms and signals generating polarized cell fates within the follicle cell layer, in understanding how vertebrate oocyte polarity impinges upon polarized follicle cell fate determination, and whether reciprocal signaling influences oocyte polarity.
Marlow FL, Mullins MC. Bucky ball functions in Balbiani body assembly and animal-vegetal polarity in the oocyte and follicle cell layer in zebrafish. 2008 Dev Biol. in press
Blaser H, Reichman-Fried M, Castanon I, Dumstrei K, Marlow FL, Kawakami K, Solnica-Krezel L, Heisenberg CP, Raz E. Migration of zebrafish primordial germ cells: a role for myosin contraction and cytoplasmic flow. 2006 Dev Cell 11(5):613-27.
Marlow F, Gonzalez EM, Yin C, Rojo C, Solnica-Krezel L. No tail co-operates with non-canonical Wnt signaling to regulate posterior body morphogenesis in zebrafish. 2004 Development. 131(1):203-16.
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. 2002 Nat Cell Biol. 4:610-15.
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. 2002 Curr Biol. 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 movements of convergence and extension. 2000 Genesis. 27(4):159-73
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. 1998 Dev Biol. 203(2):382-99
Florence Marlow's Laboratory