The people behind the papers – Baosheng Zeng and Jianjun Sun Free

Baosheng Zeng (left) and Jianjun Sun (right)

Jianjun, can you give us your scientific biography and the questions your lab is trying to answer?

JS: I carried out my PhD work in Wu-Min Deng's lab at Florida State University from 2004 to 2008. My dissertation focused on understanding how developmental signalling pathways regulate cell cycle progression in Drosophila ovaries. I then received my postdoctoral training in Allan Spradling's lab at the Carnegie Institution for Science/Howard Hughes Medical Institute, where my work illustrated the formation and function of spermathecae and parovaria: two types of glandular tissues in the Drosophila female reproductive tract. In 2013, I established my own lab in the Department of Physiology and Neurobiology, University of Connecticut, and focused on understanding the ovulation mechanism in Drosophila, which is regulated by secretions from spermathecae and parovaria, and is a poorly studied process in comparison to mammalian ovulation. In the past 10 years, we have identified multiple intrinsic factors/signalling pathways involved in Drosophila ovulation, characterised the factors promoting follicle maturation, and demonstrated the conservation between Drosophila and mammalian ovulation. Currently, our lab continues working on the ovulation mechanism, and the spermathecal and parovarian secretions that regulate sperm function, ovulation and fertilisation. Ultimately, the knowledge gained from our work will help to develop new therapeutic strategies for infertility or novel non-hormonal based contraceptives.

Baosheng, how did you come to work in the lab and what drives your research today?

BZ: I joined the Sun lab as a postdoc, following my wife, Yuping Huang, who had been a postdoc in the lab. We wanted to spend more time together while pursuing our research interests. I find the regulation of Drosophila oogenesis and ovulation both fascinating and complex, with numerous unanswered questions still to be explored. My goal in the lab is to understand the dynamic regulatory network by various transcription factors during the oogenesis and ovulation processes. Interestingly, our current work stems from an unexpected observation while examining the roles of GATA factors during ovulation. We noticed an upregulation of Serpent (Srp) in dying mid-stage egg chambers, which intrigued us. My talented undergraduate researcher, Haley Grayson, and I were eager to understand the reason behind this activation and the role of Srp in these follicle cells, which function as non-professional phagocytes under stress.

What is the background of the field that inspired your work?

JS: The field of cell death and clearance has attracted many talented scientists, who have generated enormous knowledge in the past several decades. Thanks to the work by Dr Kim McCall's lab at Boston University, we now know that Drosophila oogenesis provides an excellent model for the study of non-professional phagocytes in clearing cell debris. In addition, previous work by multiple research groups has shown that the GATA factor Srp plays a conserved and critical role in blood lineage specification, including professional phagocytes such as macrophages, especially Estee Kurant's group showing that Srp promotes the phagocytic ability of embryonic macrophages. Building on this knowledge, when we first saw that Srp is upregulated in non-professional phagocytes (follicle cells) in Drosophila ovaries, it inspired us to explore whether Srp plays a critical role in non-professional phagocytes to clear the cell debris.

Can you give us the key results of the paper in a paragraph?

JS: We aim to understand the role of the GATA factor Srp in non-professional phagocytes (follicle cells) during Drosophila oogenesis. Srp is gradually upregulated in the follicle cells of degenerating mid-stage egg chambers (DMECs), and its disruption leads to the premature death of follicle cells and incomplete clearance of germline debris after nutrient deprivation. We found that Srp acts downstream of JNK signalling to promote the phagocytic ability of follicle cells via the increase of Draper (Drpr), the phagocytic receptor, and other phagosome-processing molecules in DMECs. In addition, Srp in stretch follicle cells employs a similar mechanism to that of mid-stage follicle cells to regulate developmental cell death, which is crucial for the removal of nurse cell nuclei during late oogenesis.

Baosheng, when doing the research, did you have any particular result or eureka moment that has stuck with you?

BZ: One of the most memorable moments during this study was when we were examining late-phase degenerating mid-stage egg chambers (DMECs) and observed many egg chambers exhibiting extensive follicle cell death, along with a significant accumulation of germline debris. This was particularly exciting because the phenotype closely resembled that seen after disruption of Drpr and JNK signalling in DMECs, suggesting that Srp may be involved in regulating these known pathways. Even more intriguing was the finding that, although we were able to substantially rescue follicle cell death, the defects in germline clearance persisted. This indicates that Srp plays an important role in promoting phagocytosis in non-professional phagocytes.

And what about the flipside: any moments of frustration or despair?

BZ: During the revision process, the reviewer suggested using Dlg, a cell membrane marker, to label the membranes of stretch follicle cells (SFCs) and assess whether membrane extension remains normal after Srp knockdown. However, when we performed Dlg antibody staining, we observed that the Dlg signal itself was uneven. The outer SFC membranes showed higher intensity than the inner cells, making it difficult to draw a definitive conclusion. Ultimately, we carefully examined Drpr signals in our confocal images and compared normal SFCs with dead SFCs in srpRNAi flies.

Why did you choose to submit this paper to Development?

JS: I love Development, which is a highly recognised journal in the developmental biology field. I also like the editorial and production team, who carefully read and edit the manuscript before final publication. In fact, my first paper was published in Development in 2005. Since then, we have published multiple papers in the journal.

Baosheng, what is next for you after this paper?

BZ: We are currently working on the next story, in which we analyse the detailed roles of Srp during Drosophila ovulation, the stage following the completion of oogenesis. We hope that our current project will further enhance our understanding of the roles of GATA factors in ovulation.

Jianjun, where will this story take your lab next?

The story is exciting as it generates multiple unanswered questions. For example, is Drpr a direct target of Srp? What other direct targets does Srp regulate in the follicle cells of DMECs? What other roles does Srp play in late oogenesis? We would like to answer these questions in the near future.

Finally, let's move outside the lab – what do you like to do in your spare time?

JS: I have loved fishing from being a kid. I have fished the entire east coast of the USA, both freshwater and saltwater fishing. I find it is the best way for me to relax. I have caught more than 30 different species, including bass, walleye, chain pickle, sea trout, mackerel, black sea bass, flounder, red drum, porgy, striper, tautog, etc. I learned a lot of saltwater fishing skills from my former lab mate John Poulton, who is an excellent scientist at the University of North Carolina. I also like gardening and repairing toys/tools in my spare time.

BZ: In my spare time, I enjoy fishing with my family, a hobby inspired by my supervisor, Jianjun. Last year, my wife and I caught more than 100 fish, including crappies, bass, bluegill and pike – it was a lot of fun! I also enjoy running; my wife and I previously participated in the Boston half marathon. Additionally, I incorporate rope jumping into my workouts to stay active.