Developmental Biology
Ozbudak Lab

Ozbudak Research Lab

Our overriding interest is to achieve a systems-level understanding of embryonic development and pattern formation by integrating quantitative experiments with mathematical modeling. Embryos develop spatiotemporal patterns by encoding and interpreting biological signals in real time. Despite unavoidable fluctuations in gene expression, embryonic development is robust and reproducible, which necessitates several mechanisms buffering stochastic gene expression.

A striking example of robust spatiotemporal patterning is the rhythmic segmentation of somites, which are precursors of the vertebral column. Segmentation of somites is controlled by: 1) the oscillatory expression of the Hes/Her gene family, known as the vertebrate segmentation clock, 2) short-distance Notch signaling, 3) long-distance Fgf, Wnt, and Retinoic Acid (RA) signaling gradients and 4) a network of transcription factors integrating outputs of the segmentation clock and the signaling pathways.

We combine single-cell microscopy measurements, time-resolved perturbation experiments, genome-wide techniques, biophysical modeling and computational simulations to decipher the mechanism underlying robust spatiotemporal pattern formation and cell fate determination.

Publications

Simsek, MF; Chandel, AS; Saparov, D; Zinani, OQ H; Clason, N; Özbudak, EM. Periodic inhibition of Erk activity drives sequential somite segmentation. Nature. 2023; 613:153-159.

Zinani, OQ H; Keseroglu, K; Ay, A; Özbudak, EM. Pairing of segmentation clock genes drives robust pattern formation. Nature. 2021; 589:431-436.

Keskin, S; Simsek, MF; Vu, HT; Yang, C; Devoto, SH; Ay, A; Özbudak, EM. Regulatory Network of the Scoliosis-Associated Genes Establishes Rostrocaudal Patterning of Somites in Zebrafish. iScience. 2019; 12:247-259.

Simsek, MF; Özbudak, EM. Spatial Fold Change of FGF Signaling Encodes Positional Information for Segmental Determination in Zebrafish. Cell Reports. 2018; 24:66-78.e8.

Keskin, S; Devakanmalai, GS; Kwon, SB; Vu, HT; Hong, Q; Lee, YY; Soltani, M; Singh, A; Ay, A; Özbudak, EM. Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling. Cell Reports. 2018; 23:2175-2185.e4.

Devakanmalai, GS; Zumrut, HE; Özbudak, EM. Cited3 activates Mef2c to control muscle cell differentiation and survival. Biology Open. 2013; 2:505-514.

Özbudak, EM; Tassy, O; Pourquié, O. Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation. Proceedings of the National Academy of Sciences of USA. 2010; 107:4224-4229.

Gomez, C; Özbudak, EM; Wunderlich, J; Baumann, D; Lewis, J; Pourquié, O. Control of segment number in vertebrate embryos. Nature. 2008; 454:335-339.

Özbudak, EM; Lewis, J. Notch signalling synchronizes the zebrafish segmentation clock but is not needed to create somite boundaries. Editor, Mullins M. PLoS Genetics. 2008; 4:e15.

Ozbudak, EM; Thattal, M; Lim, HH; Shraiman, BI; Van Oudenaarden, A. Multistability in the lactose utilization network of Escherichia coli. Nature. 2004; 427:737-740.

Ozbudak, EM; Thattai, M; Kurtser, I; Grossman, AD; Van Oudenaarden, A. Regulation of noise in the expression of a single gene. Nature Genetics. 2002; 31:69-73.

Keseroglu, K; Zinani, OQ H; Keskin, S; Seawall, H; Alpay, EE; Özbudak, EM. Stochastic gene expression and environmental stressors trigger variable somite segmentation phenotypes. Nature Communications. 2023; 14:6497.

Simsek, MF; Özbudak, EM. A design logic for sequential segmentation across organisms. FEBS Journal. 2023; 290:5086-5093.

Chandel, AS; Stocker, M; Özbudak, EM. The Role of Fibroblast Growth Factor Signaling in Somitogenesis. DNA and Cell Biology. 2023; 42:580-584.

Keseroglu, K; Zinani, OQ H; Özbudak, EM. Using single-molecule fluorescence in situ hybridization and immunohistochemistry to count RNA molecules in single cells in zebrafish embryos. STAR Protocols. 2023; 4:102020.

Simsek, MF; Özbudak, EM. Human stem cell models unravel mechanisms of somite segmentation. Cell Stem Cell. 2023; 30:246-247.

Simsek, MF; Chandel, AS; Saparov, D; Zinani, OQ H; Clason, N; Özbudak, EM. Periodic inhibition of Erk activity drives sequential somite segmentation. Nature. 2023; 613:153-159.

Simsek, MF; Özbudak, EM. Patterning principles of morphogen gradients. Open Biology. 2022; 12:220224.

Zinani, OQ H; Keseroglu, K; Dey, S; Ay, A; Singh, A; Özbudak, EM. Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes. iScience. 2022; 25:104579.

Zinani, OQ H; Keseroglu, K; Özbudak, EM. Regulatory mechanisms ensuring coordinated expression of functionally related genes. Trends in Genetics. 2022; 38:73-81.

Simsek, MF; Özbudak, EM. A 3-D Tail Explant Culture to Study Vertebrate Segmentation in Zebrafish. Jove-Journal of Visualized Experiments. 2021; 2021.

Zinani, OQ H; Keseroglu, K; Ay, A; Özbudak, EM. Pairing of segmentation clock genes drives robust pattern formation. Nature. 2021; 589:431-436.

Keskin, S; Simsek, MF; Vu, HT; Yang, C; Devoto, SH; Ay, A; Özbudak, EM. Regulatory Network of the Scoliosis-Associated Genes Establishes Rostrocaudal Patterning of Somites in Zebrafish. iScience. 2019; 12:247-259.

Simsek, MF; Özbudak, EM. Spatial Fold Change of FGF Signaling Encodes Positional Information for Segmental Determination in Zebrafish. Cell Reports. 2018; 24:66-78.e8.

Keskin, S; Devakanmalai, GS; Kwon, SB; Vu, HT; Hong, Q; Lee, YY; Soltani, M; Singh, A; Ay, A; Özbudak, EM. Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling. Cell Reports. 2018; 23:2175-2185.e4.

Contact Us

Ozbudak
For more information or to learn about joining our team, please email:  ertugrul.ozbudak@cchmc.org