Mansi Srivastava

Professor of Organismic and Evolutionary Biology
Curator of Invertebrate Zoology in the Museum of Comparative Zoology

Most animals are able to repair wounds and many can regenerate extensively, re-growing organs or even entire body plans from small fragments. Very little is known about how wounding results in repair and/or regeneration, or whether these mechanisms are similar across diverse animal species. We are taking an integrative approach for studying the wound response and stem cell biology during regeneration in an evolutionary framework by using a broad range of techniques including transcriptional profiling and lineage tracing.

We have developed the three-banded panther worm, Hofstenia miamia, as a new model acoel species for studies of regeneration. Acoels are likely to be the earliest lineage of animals with bilateral symmetry (bilaterians), and are therefore phylogenetically well-placed to inform questions about the evolution of regenerative mechanisms. Studies of Wnt and Bmp signaling pathways inHofstenia regeneration revealed that the mechanisms for patterning new tissue along the anterior-posterior and dorsal-ventral axes are conserved between acoels and planarians, a bilaterian lineage that is distantly related to acoels. This finding raises the possibility that highly conserved molecular genetic processes could underlie other aspects of regeneration, such as the regulation of stem cell differentiation or renewal.

We are using the many advantages of Hofstenia as a model regenerative species (e.g., robust regeneration capacity, RNAi that can be administered by soaking, tools for studying gene function, ability to isolate stem cells) to identify genes that control regeneration. Hofstenia produces accessible embryos that enable comparisons of regeneration and development, and provide a unique opportunity to use gene-delivery and genome-editing tools to study regeneration. Furthermore, these studies will complement those in other regenerative systems and enable us to identify conserved mechanisms. Because essential components of a process tend to be conserved over the course of evolution, identifying regenerative pathways shared by many species would be a powerful method to uncover as yet unknown regulators of regeneration.

Recent Publications

J.O. Kimura, D.M. Bolanos Rodriguez, L. Ricci, and M. Srivastava. Embryonic origins of adult pluripotent stem cells. Cell, 185:4756-4769, 2022.

R.E. Hulett, J. O. Kimura, D.M. Bolanos Rodriguez, Y-J. Luo, C. Rivera-Lopez, L. Ricci, and M. Srivastava. Acoel single cell atlas reveals expression dynamics and heterogeneity of a pluripotent stem cell population. BioRxivhttps://doi.org/10.1101/2022.02.10.479464, 2022.

L. Ricchi and M. Srivastava. Transgenesis in the acoel worm Hofstenia miamia. Dev. Cell, 56:3160–3170, doi: 10.1016/j.devcel.2021.10.012, 2021.

M. Srivastava. Beyond casual resemblance: Rigorous frameworks for comparing regeneration across species. Ann. Rev. Cell Dev. Biol., 37:415–440, doi.org/10.1146/annurev-cellbio-120319-114716, 2021.

J.O. Kimura, L. Ricci, and M. Srivastava. Embryonic development in the acoel Hofstenia miamia. Development, 148:dev188656, 2021.

A.N. Ramirez, K. Loubet-Senear, and M. Srivastava. A regulatory program for initiation of wnt signaling during posterior regeneration. Cell Reports, 32:108098, 2020.

R.E. Hulett, D. Potter, and M. Srivastava. Neural architecture and regeneration in the acoel Hofstenia miamia. Proc. R. Soc. B, 287:20201198, 2020.