Planarian flatworms have an exceptional ability to undergo whole-body regeneration. Although this observation has fascinated scientists for centuries, the long-standing question of how this is accomplished remains to be completely understood. One determinant of planarian regeneration is the timely establishment of regeneration polarity at the wound site. Anterior facing wounds regenerate the head whereas posterior facing wounds regenerate the tail- this is known as regeneration polarity. Anterior polarity, for example, is determined by the expression of the Wnt antagonist notum at the anterior facing wound. This process is then followed by anterior-pole determination. The anterior pole is the Spemann-Mangold organizer equivalent in planarians. Therefore, precise spatial and temporal determination of this pole is necessary for the head regeneration as well as patterning of different tissues within the head primordia.
Planarian muscles, in addition to their canonical roles in locomotion and skeletal support, predominantly express all the pole markers and morphogens associated with positional information establishment and patterning. Furthermore, muscles in planarians also act as âstructural scaffoldsâ for organ regeneration and also function like connective tissue by expressing many of the matrisome related genes. Thus, given this multifaceted role of muscles, defect in muscle organization or loss of muscle-associated factors inadvertently leads to defective regeneration. Although what underlies this functional versatility of planarian muscles is poorly understood.
Here, we report the function of DDX24, a D-E-A-D Box RNA helicase, in planarian regeneration. Combinatorial RNA-FISH revealed that ddx24 was expressed in a subset of naive stem cells, stem cells primed for muscle fate, and in the differentiated muscles. We custom generated a polyclonal antibody against DDX24 and found that the protein was particularly enriched in longitudinal muscle fibers. Knockdown of ddx24 resulted in muscle fiber disorganization and abnormal expression of pole markers suggesting a defect in pole regeneration. Loss of DDX24 also resulted in gross misregulation of many well-characterized muscle-expressed positional control genes and morphogens like wnt1. Although canonical Wnt signaling is known to specify tail fate across Bilateria, in planarians, amputation induces the expression of wnt1 in posterior as well as in anterior blastema at early time points of regeneration. However, during later stages of regeneration, this expression persists only in the posterior blastema. Surprisingly, in ddx24 knockdown animals, wnt1 levels remain ectopically upregulated both in the posterior and anterior regenerating tissues. Modulating this Wnt activity by knocking-down various Wnt pathway genes, in a ddx24 RNAi background, partially rescued the regeneration defect. Therefore, it is likely that DDX24 negatively regulates the wound-induced Wnt activity required for the specification of the signaling centers during regeneration.
References:
1. DDX24, a D-E-A-D box RNA helicase, is required for muscle fiber organization and anterior pole specification essential for head regeneration in planarians.
bioRxiv DOI: https://doi.org/10.1101/2021.01.21.427618
Souradeep R. Sarkar, Vinay Kumar Dubey, Anusha Jahagirdar, Vairavan Lakshmanan, Mohamed Mohamed Haroon, Sai Sowndarya, Ramanathan Sowdhamini, Dasaradhi Palakodeti.
2. Mitochondrial state determines functionally divergent stem cell population in planaria.
Stem Cell Reports. DOI: https://doi.org/10.1016/j.stemcr.2021.03.022
Mohamed Mohamed Haroon, Vairavan Lakshmanan, Souradeep R. Sarkar, Kai Lei, Praveen K Vemula, Dasaradhi Palakodeti.
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