Developmental Genetics of Zebrafish

My lab studies inner ear development in zebrafish. A prominent feature of our research is to investigate how cell-cell signaling and downstream gene-interactions control development.  One project in the lab focuses on how cell signaling regulates ectodermal patterning during gastrulation to establish the otic placode, the precursor of the inner ear.  Our recent work shows that localized Fgf signaling is especially critical for inducing formation of the otic placode, and members of the Pax2/5/8 family of transcription factors are important mediators of Fgf signaling.  During later stages of inner ear development, we are exploring how sensory hair cells and neurons are regulated.  Our studies address how these cells initially form, how they are genetically maintained, and how they become specialized for hearing vs. balance.  We are also investigating how zebrafish can replace dead and damaged hair cells, an ability that mammals have lost.  The inability to regenerate hair cells explains why humans show progressive irreversible hearing loss as we age.  It is hoped that activating or augmenting human homologs of genes shown to operate in zebrafish might help restore hearing and balance in humans.

1. Roberson, W, Holland, JN, Riley, BB. Pax2a, Pax5 and Cdh1-β-catenin, but not Wnt, protect sensory hair cells from destabilizing effects of fgf signaling on cell adhesion. Dev Biol. 2024;517 :157-167. doi: 10.1016/j.ydbio.2024.09.009. PubMed PMID:39332789 .
2. Tan, AL, Mohanty, S, Guo, J, Lekven, AC, Riley, BB. Pax2a, Sp5a and Sp5l act downstream of Fgf and Wnt to coordinate sensory-neural patterning in the inner ear. Dev Biol. 2022;492 :139-153. doi: 10.1016/j.ydbio.2022.10.004. PubMed PMID:36244503 .
3. Riley, BB. Comparative assessment of Fgf's diverse roles in inner ear development: A zebrafish perspective. Dev Dyn. 2021;250 (11):1524-1551. doi: 10.1002/dvdy.343. PubMed PMID:33830554 .
4. Kantarci, H, Gou, Y, Riley, BB. The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle. Elife. 2020;9 :. doi: 10.7554/eLife.56301. PubMed PMID:32338604 PubMed Central PMC7253172.
5. Gou, Y, Vemaraju, S, Sweet, EM, Kwon, HJ, Riley, BB. sox2 and sox3 Play unique roles in development of hair cells and neurons in the zebrafish inner ear. Dev Biol. 2018;435 (1):73-83. doi: 10.1016/j.ydbio.2018.01.010. PubMed PMID:29355523 PubMed Central PMC5818298.
6. Gou, Y, Guo, J, Maulding, K, Riley, BB. sox2 and sox3 cooperate to regulate otic/epibranchial placode induction in zebrafish. Dev Biol. 2018;435 (1):84-95. doi: 10.1016/j.ydbio.2018.01.011. PubMed PMID:29355522 PubMed Central PMC5818308.
7. Kantarci, H, Gerberding, A, Riley, BB. Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle. Proc Natl Acad Sci U S A. 2016;113 (44):E6840-E6848. doi: 10.1073/pnas.1609146113. PubMed PMID:27791112 PubMed Central PMC5098670.
8. Kantarci, H, Edlund, RK, Groves, AK, Riley, BB. Tfap2a promotes specification and maturation of neurons in the inner ear through modulation of Bmp, Fgf and notch signaling. PLoS Genet. 2015;11 (3):e1005037. doi: 10.1371/journal.pgen.1005037. PubMed PMID:25781991 PubMed Central PMC4364372.
9. Maulding, K, Padanad, MS, Dong, J, Riley, BB. Mesodermal Fgf10b cooperates with other fibroblast growth factors during induction of otic and epibranchial placodes in zebrafish. Dev Dyn. 2014;243 (10):1275-85. doi: 10.1002/dvdy.24119. PubMed PMID:24677486 PubMed Central PMC4313390.
10. Edlund, RK, Ohyama, T, Kantarci, H, Riley, BB, Groves, AK. Foxi transcription factors promote pharyngeal arch development by regulating formation of FGF signaling centers. Dev Biol. 2014;390 (1):1-13. doi: 10.1016/j.ydbio.2014.03.004. PubMed PMID:24650709 PubMed Central PMC4013273.
11. Holloway, N., Riley, B. and MacKenzie, D. (2021). Expression of the sodium iodide symporter (NIS) in reproductinve and neural tissues in teleost fish. Gen. Comp. Enochrinol. 300, 113632.
12. Vonica, A., Bhat, N., Phan, K., Guo, J., Iancu, L., Wber, J. A., Karger, A., Cain, J. W., Wang, C. E., DeStefano, G. M., O’Donnell-Luria, A. H., Christiano, A. M., Riley, B., Butler, S. J. and Luria, B. (2020). APCDD1 is a dual BMP/WNT inhibitor in the developing nervous system and skin. Dev. Biol. 464(1), 71-87. PMCID:PMC7307705.