Skip Ribbon Commands
Skip to main content
Researchers
  • Dr.  Yaniv Elkouby
dr. Yaniv Elkouby
 
Cell and developmental biology of early oogenesis
Cell and developmental biology of early oogenesis

Our Research

Cell and developmental biology of early oogenesis in zebrafish

Our lab investigates cellular mechanisms of early oocyte differentiation, from the stem cell to the follicle. Germ cells are at the basis of reproduction and undergo fascinating processes during their development. Unlike many other tissues where cells perform a collective tissue function, germ cells differentiate in the gonad to perform an individual function. The oocyte gives rise to the egg, a single cell that contains the building blocks that initiate the early events of embryonic development following fertilization.
The oocyte undergoes a dramatic differentiation process (Figure 1) that begins when germline stem cells divide and produce the oogonia, a mitotic precursor cell of the differentiating meiotic oocyte. Oogonia divide incompletely to generate early oocytes that are inter-connected to sister oocytes via cytoplasmic bridges in a cellular organization called the germline cyst. Meiosis initiation transforms the oogonia in the cyst into differentiating oocytes that then separate and become surrounded by somatic granulosa cells in the follicle. In the early differentiating oocyte dramatic nuclear events underlie meiosis, while the cytoplasm in most species becomes polarized. Notably, these intracellular processes occur simultaneously with the changes in cellular organization, all while the oocyte significantly grows in volume.
Figure 1. The primary events of early oogenesis that we investigate are mostly conserved between zebrafish and mammals. Blue bars indicate zebrafish processes, light blue bar indicate mouse processes, and dark blue bars indicate common processes.
Figure 1. The primary events of early oogenesis that we investigate are mostly conserved between zebrafish and mammals. Blue bars indicate zebrafish processes, light blue bar indicate mouse processes, and dark blue bars indicate common processes.

The Centrosome Organizing Center (COC) at a nexus of early oogenesis

How are these events mechanistically executed and controlled? How are they collectively coordinated by the cell in time and space? How are they developmentally coordinated across cells? We have discovered a novel cellular organizer that we termed the Centrosome Organizing Center (COC) (Figure 2).
Figure 2. Zooming in on early oogenesis: From the fish, into the ovary, the germline cyst and oocyte sub-cellular mechanisms. Our discovery of the Centrosome Organizing Center (COC).
Figure 2. Zooming in on early oogenesis: From the fish, into the ovary, the germline cyst and oocyte sub-cellular mechanisms. Our discovery of the Centrosome Organizing Center (COC).
The COC integrates multiple cellular processes such as mitosis (Figure 3), meiosis (Figure 4A), cell polarity (Figure 4B), prion-like mechanisms (Figure 5), mechanical regulation and ciliary functions (Figure 6) in the oocyte.
Figure 3. The COC and mitosis. The active COC localizes adjacent to the cytoplasmic bridge of sister oocytes (Left), and likely positioned by the plane of the last mitotic division in the cyst.
Figure 3. The COC and mitosis. The active COC localizes adjacent to the cytoplasmic bridge of sister oocytes (Left), and likely positioned by the plane of the last mitotic division in the cyst.
Figure 4. The COC simultaneously coordinates meiotic chromosomal pairing (left), and symmetry breaking in cellular polarization of the oocyte (right).
Figure 4. The COC simultaneously coordinates meiotic chromosomal pairing (left), and symmetry breaking in cellular polarization of the oocyte (right).
Figure 5. The COC (centrosome) organizes the formation of the Blabiani body, a universal oogenesis structure that further polarizes the oocyte. Balbiani body formation by aggregation, nucleation and maturation utilizes prion-like mechanisms
Figure 5. The COC (centrosome) organizes the formation of the Blabiani body, a universal oogenesis structure that further polarizes the oocyte. Balbiani body formation by aggregation, nucleation and maturation utilizes prion-like mechanisms.
Figure 6. The COC (Gamma Tub) connects to a novel oocyte cytoskeletal structure that resembles the primary cilium (Ac. Tub), specifically at zygotene stages (when the COC coordinates chromosomal pairing and the symmetry braking)
Figure 6. The COC (Tub) connects to a novel oocyte cytoskeletal structure that resembles the primary cilium (Ac. Tub), specifically at zygotene stages (when the COC coordinates chromosomal pairing and the symmetry braking).

Our current investigation of the COC

We use advanced genetics and quantitative microscopy in zebrafish, as well as experiments in live cultured ovaries to study the mechanisms of the COC and its regulation in each process. Furthermore, the investigation of the COC allows us to study how these multiple programs are coordinated by the cell on a single platform. We additionally developed a method for stage specific proteomics to identify novel factors in the early oocyte.
Altogether, we aim to construct a comprehensive mechanistic view of early oogenesis. The early processes we investigate are conserved between zebrafish and mammals, but in humans, early oogenesis occurs in fetal development and determines the number of oocytes for a female lifespan. Our investigation will advance our understanding of women reproduction and health.

Publications

Elkouby YM. All in one - integrating cell polarity, meiosis, mitosis and mechanical forces in early oocyte differentiation in vertebrates. Int J Dev Biol. 2017;61(3-4-5):179-93. *Invited review (peer reviewed).Link
Elkouby YM, Mullins MC. Coordination of cellular differentiation, polarity, mitosis and meiosis - New findings from early vertebrate oogenesis. Dev Biol. 2017;430(2):275-87. **Back-to-back. Link
Elkouby YM, Mullins MC. Methods for the analysis of early oogenesis in zebrafish. Dev Biol. 2017;430(2):310-24. **Back-to-back. Link
Escobar-Aguirre M., Elkouby YM, Mullins MC. (2017) Localization in oogenesis of maternal regulators of embryonic development. Adv. Exp. Med. Biol. 953, 173–207. *Book chapter. Link
Elkouby YM, Jamieson-Lucy A, Mullins MC (2016) Oocyte Polarization Is Coupled to the Chromosomal Bouquet, a Conserved Polarized Nuclear Configuration in Meiosis. PLoS Biology 14(1): e1002335. doi:10.1371/journal.pbio.1002335. Link
*Featured as a highlight in: Schubert (2016) World of Reproduction: A bouquet for oocyte polarity. Biology of Reproduction. doi: 10.1095/biolreprod.116.139105. Link
Elkouby YM, Polevoy H, Gutkovich YE, Michaelov A and Frank D. (2012) A hindbrain repressive Wnt3a/Meis3/Tsh1 circuit promotes neuronal differentiation and coordinates tissue maturation. Development 139, 1487-1497.
Fonar Y, Gutkovich YE, Root H, Malyarova A, Aamar E, Golubovskaya VM, Elias S, Elkouby YM, Frank D. (2011) Focal Adhesion Kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate. Molecular Biology of the Cell. 2011 Jul;22(13):2409-21
Elkouby YM and Frank D. (2010) Wnt/β-catenin signaling in vertebrate posterior neural development. Morgan & Claypool Life Sciences Publishers Series, Developmental Biology, Book #4, USA. *Book.
Gutkovich YE, Ofir R, Elkouby YM, Dibner C, Gefen A, Elias S, Frank D. (2010) Xenopus Meis3 protein lies at a nexus downstream to Zic1 and Pax3 proteins, regulating multiple cell-fates during early nervous system development. Developmental Biology. 2010 Feb 1; 338 (1): 50-62.
Elkouby YM, Elias S, Casey SE, Blythe SA, Tsabar N, Klein PS, Liu LJ and Frank D. (2010) Mesodermal Wnt signaling organizes the neural plate via Meis3. Development 137, 1531-1541.
​​​​​​
website by Bynet Software Systems