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Jia L. Song, Ph.D.
BISC 615 Developmental Biology
BISC 207 Introductory Biology
The potential for forming a new organism begins at fertilization, when the sperm meets the egg. Across species from the worm to the human, development of the newly fertilized egg to a juvenile or an adult requires the careful regulation of cell growth, differentiation, and morphogenesis. Different cell types make different sets of proteins, even when their genomes are identical. What makes each cell type unique is a direct result of differential gene expressions mediated by transcription factors and signaling molecules in response to chemicals and proteins in the cell and the environment. Dysregulation of important genes involved in developmental decisions can lead to human diseases. Our research addresses one of the fundamental questions in developmental biology: How are genes regulated during early development?
My laboratory investigates the regulatory roles of microRNAs (miRNAs) in early development. miRNAs are a class of non-coding RNA molecules that have recently been discovered to repress gene expressions in animal cells. miRNAs are critical for many aspects of life, including the development of an organism and physiological functions of cells and tissues.
We established the use of the sea urchin embryo as an animal model to elucidate how miRNAs control gene regulatory networks (GRNs) and signaling transduction pathways that drive developmental programs, pattern formation, and cell motility in an embryo. The sea urchin model has an exceptionally well-studied GRN and most of its miRNA families consist of a single species, which makes it amenable to unique, powerful functional analysis. Integrating state-of-the-art proteomics, bioinformatics, and molecular analyses, my research has revealed the function of miRNAs as integrators of developmental pathways. Since miRNAs, GRNs, and signaling pathways are evolutionarily highly conserved, our research serves as a paradigm of understanding the general function of miRNAs as important integrators of GRNs and signaling pathways to power development in making a functional embryo.
Our research areas are:
1. miRNAs modulate signaling transduction pathways to impact early development
Signaling transduction pathways are critical in early development, yet the role of miRNA regulation of these pathways is still lacking. Both Wnt and Delta/Notch signaling pathways are evolutionarily highly conserved and important in cell specification and differentiation. The goal of this project is to understand how miRNAs regulate these signaling pathways, and the impact of miRNA regulation in development.
2. miRNAs suppress genes of cell motility to control embryonic organization
We have previously established that microRNA-31 (miR-31) is one of the four critical miRNAs necessary to rescue developmental defects induced by the knockdown of miRNA biogenesis enzymes, indicating its importance in early development. As part of our goal to define miR-31’s function in the embryo, we bioinformatically searched for miR-31 targets genome-wide and compared the proteome of normal and miR-31 knockdown embryos, since animal miRNAs typically mediate their gene targets by translational repression. From these analyses, we identified that several genes that control cell motility were regulated by miR-31, including a small GTPase Arf6. We have shown that Arf6 protein was increased in miR-31 knockdown embryos compared to the control, indicating that miR-31 suppresses Arf6. Based on these results, we hypothesized that miR-31 suppresses genes that mediate the mechanics of cell motility.
3. miRNAs cross-regulate gene regulatory networks and signaling pathways
miR-31 plays a key role in development and diseases by regulating genes important for cell differentiation, proliferation, apoptosis, and cell motility. However, miR-31 has been examined mostly in the context of cancer, and its role in development needs to be better understood. The goal of this project is to advance our understanding of how miR-31 integrates and cross-regulates GRNs and signaling pathways to impact development.
Current funding sources:
- NSF CAREER Award # IOS-1553338 (2016-2021)
- NIH 1P20GM10365301 (2013-2016)
- Delaware Bioscience Center for Advanced technology (2015-2016)
- Nadezda Stepicheva - Postodoctoral Fellow
- Nina Sampilo-MS student
- Michael Testa-Undergraduate Researcher
- Alexander George-Undergraduate Researcher
- Chelsea Lee-Undergraduate Researcher
- Nadezda Stepicheva - Ph.D. 2016
- Priscilla Kobi - MS, 2016
- Santiago Suarez - MS, 2015
- Priya Nigam - MS, 2013
- Archana Siddam -MS, 2012
- Undergraduate researcher with Thesis: Lydia Bonar (2011), Megan Dumas (2013), Kelsie Landis (2014), Carissa McKinney (2014), Tyler McCann (2016)
- Stepicheva, N., M. Dumas, P. Kobi, J. Donaldson, and J.L. Song (2016) The small GTPase Arf6 regulates sea urchin cellular morphogenesis. Differentiation. In Revision
- Stepicheva, N.A. and J.L. Song (2016) Function and regulation of microRNA-31 in development and disease. Molecular Reproduction and Development. Jul 12. doi: 10.1002/mrd.22678. PMID:27405090
- Stepicheva, N.A. and J.L. Song (2015) miR-31 modulates skeletogenic cell patterning in the sea urchin embryos. Development.Sep 23. pii: dev.127969. PMID:26400092
- Song, J.L, P. Nigam, S. Tektas, and E. Selva (2015) microRNA regulation of Wnt signaling pathways in development and disease. Cellular Signaling. 2015 Jul;27(7):1380-1391. doi: 10.1016/j.cellsig.2015.03.018. Epub 2015 Apr 2. Review. PubMed PMID: 25843779; PubMed Central PMCID: PMC4437805.
- Stepicheva, N, Nigam P.A., Siddam A., Peng, CF, J. L. Song (2015) microRNAs regulate β-catenin of the Wnt signaling pathway in early sea urchin development. Developmental Biology. Jan 19. Pii: S0012-1606 (15)00016-0. Doi:10.1016/j.ydbio.2015.01.008. PMID: 25614238.
- Song, J.L. (2014) Broad distribution of ARF6 in somatic and germ cells of the sea urchin ovary. Molecular Reproduction and Development. March 29. doi: 10.1002/mrd.22326. PMID:24687463
- Stepicheva, N. and J.L. Song. (2014) High throughput microinjections of sea urchin zygotes. Journal of Visualized Experiments. Jan 21;(83). doi: 10.3791/50841.
- Yajima, M., Gustafson, E.A., J.L. Song, and G.M. Wessel. (2013) Piwi regulates Vasa accumulation during embryogenesis in the sea urchin. Developmental Dynamics. Nov 12. doi: 10.1002/dvdy.24096.
- Oulhen N, Yoshida T, Yajima M, Song J.L., Sakuma T, Sakamoto N, Yamamoto T, Wessel GM. (2013) The 3'UTR of nanos2 directs enrichment in the germ cell lineage of the sea urchin. Developmental Biology. Jan 25. doi: 10.1016/j.ydbio.2013.01.019.
- Song J.L. and Wessel GM.(2012) The forkhead transcription factor FoxY regulates Nanos. Molecular Reproduction and Development. Oct; 79(10):680-8.
- Song J.L., Stoeckius M, Maaskola J, Friedlaender M, Stepicheva N, Juliano C, Lebedeva S, Thompson W, Rajewsky N, Wessel GM. (2012) Select microRNAs are essential for early development in the sea urchin. Developmental Biology. 362(1):104-13. Epub 2011 Dec 3.
- Wessel GM, Juliano CE, Wong J, Gustafson E, Song J.L. (2009) Molecular markers of oocyte and primordial germ cell development in the sea urchin. Echinoderms. 2009:517‐528.
- Voronina, E, M. Lopez, C. Juliano, E. Gustafson, J.L. Song, C, Extavour, S. George, P. Oliveri, D. McClay, and G. M. Wessel (2008) Vasa protein expression is restricted to the small micromeres of the sea urchin, but is inducible in other lineages early in development. Developmental Biology. 314(2):276–286.
- Song J.L., Wessel GM. (2007) Genes involved in the RNA interference pathway are differentially expressed during sea urchin development. Developmental Dynamics. 236(11):3180–3190.
- Sodergren E, Weinstock GM, Davidson EH, et al. (2006) The genome of the sea urchin Strongylocentrotus purpuratus. Science.314(5801):941–952.
- Song J.L., Wong J.L., Wessel GM. (2006) Oogenesis: single cell development and differentiation. Developmental Biology. 300(1):385–405.
Education outreach at the Delaware Children Museum.
(A) Graduate student Stepicheva shows child and parent our animals for developmental studies.
(B) A child checks out the animals.
Collaboration with Professor Gallo-Fox in Early Childhood Education.
Phone: (302) 831-2794
Fax: (302) 831-2281
Office: 323 Wolf Hall
Lab: 018 Wolf Hall
Department of Biological Sciences
University of Delaware
Newark, DE 19716
- B.S. - Cornell University
- Ph.D. - University of Washington
- Postdoctoral - Brown University