Biology subjects

Clay, K. B.

Publications and source records attributed to Clay, K. B..

3 recordsLinked to original sources

bioRxiv2026

Syntaxin-1 and syntaxin binding protein 1-1 are required for planarian behavior and brain regeneration

Background: Nervous system regeneration requires creation of new neurons and their integration into new and existing networks. How new neurons find their targets and reconnect in the environment of regenerating tissue remains a major gap in knowledge. The planarian Schmidtea mediterranea is well suited to the study of neural regeneration due to the remarkable ability of planarians to regenerate their entire body, including the nervous system. However, we have not yet been able to explore synaptogenesis in regeneration using planarians due to a lack of tools to study synapses. Here we investigate potential players in planarian synapse, focusing on the conserved syntaxin protein family, which functions in neurotransmitter vesicle fusion at the synapse. Results: We found that reduction of either syntaxin-1 (stx1) or syntaxin-binding protein 1-1 (stxbp1-1) decreased locomotion and impeded brain regeneration, specifically in synapse-rich regions. Conclusions: Our observations support STX-1 and STXBP1-1 as bona fide synapse components, providing a starting point for studies neuronal connectivity during homeostatic remodeling and regeneration.

neuroscience↗

bioRxiv2025

Combinatorial mechanisms specify cellular location and neurotransmitter identity during regeneration of planarian neurons

During regenerative neurogenesis, neurons must be created in the right types and locations. Though regenerative neurogenesis is limited in humans, other animals use regenerative neurogenesis to faithfully restore form and function after brain injury. Planarians are flatworms with extraordinary capacity for brain regeneration. Planarians use pluripotent stem cells to create neurons after injury, rather than resident progenitors. In this context, genetic mechanisms that produce diverse neurons with correct local identity remain unknown. Here, we report the discovery of factors important for regenerative neurogenesis of dopaminergic neurons in the planarian central, peripheral, and pharyngeal nervous systems. Distinct genes promote dopaminergic neuronal identity and instruct neurons to inhabit regions of the nervous system. Our results demonstrate that planarian neuronal fate requires factors that simultaneously direct neurotransmitter choice and regional location. Our work suggests that combinatorial direction of cell type could inform and improve exogenous stem cell therapies aimed at precisely replacing neurons.

neuroscience↗

bioRxiv2023

Planarian LDB and SSDP proteins scaffold transcriptional complexes for regeneration and patterning

Sequence-specific transcription factors often function as components of large regulatory complexes. LIM-domain binding protein (LDB) and single-stranded DNA-binding protein (SSDP) function as core scaffolds of transcriptional complexes in animals and plants. Little is known about potential partners and functions for LDB/SSDP complexes in the context of tissue regeneration. In this work, we find that planarian LDB1 and SSDP2 promote tissue regeneration, with a particular function in mediolateral polarity reestablishment. We find that LDB1 and SSDP2 interact with one another and with characterized planarian LIM-HD proteins Arrowhead, Islet1, and Lhx1/5-1. SSDP2 and LDB1 also function with islet1 in polarity reestablishment and with lhx1/5-1 in serotonergic neuron maturation. Finally, we show new roles for LDB1 and SSDP2 in regulating gene expression in the planarian intestine and parenchyma; these functions may be LIM-HD-independent. Together, our work provides insight into LDB/SSDP complexes in a highly regenerative organism. Further, our work provides a strong starting point for identifying and characterizing potential binding partners of LDB1 and SSDP2 and for exploring roles for these proteins in diverse aspects of planarian physiology.

developmental biology↗