Smed-pou4-2 regulates mechanosensory neuron regeneration and function in planarians
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eLife Assessment
This is a valuable study that explores the role of the conserved transcription factor POU4-2 in the maintenance, regeneration, and function of planarian mechanosensory neurons. The authors provide solid evidence provided by gene expression and functional studies to demonstrate that POU4-2 is required for the maintenance and regeneration of functional mechanosensory neurons in planarians. Furthermore, the authors identify conserved genes associated with human auditory and rheosensory neurons as potential targets of this transcription factor.
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Abstract
Abstract
POU4 homologs are involved in the development of sensory cell types across diverse species, including cnidarians, ascidians, and mammals. Whether these developmental regulators are reused during adult tissue maintenance and regeneration remains a fundamental question in regenerative biology. Here, we investigate the role of the Schmidtea mediterranea BRN3/POU4 homolog, Smed-pou4-2 (pou4-2), in the regeneration of mechanosensory neurons. We find that pou4-2 is regulated by the SoxB1 homolog, soxB1-2, and is expressed in a distinct population of ciliated sensory cells that detect water flow. Transcriptomic analysis of pou4-2-deficient planarians reveals enrichment for conserved genes associated with human auditory and vestibular function, suggesting that planarian rheosensory neurons share molecular features with mammalian inner ear hair cells. Expression of these conserved genes is abrogated by RNAi-mediated knockdown of pou4-2. To determine whether these transcriptional changes had functional consequences for mechanosensory neuron identity or behavior, we next assessed the impact of pou4-2 knockdown on sensory function. pou4-2 RNAi results in impaired mechanosensation in both uninjured and regenerating planarians. Together with the loss of terminal differentiation markers in mechanosensory neurons, these findings identify Smed-pou4-2 as a key regulator of mechanosensory neuron identity in planarians and support the idea that conserved sensory specification programs are redeployed during adult tissue regeneration.
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eLife Assessment
This is a valuable study that explores the role of the conserved transcription factor POU4-2 in the maintenance, regeneration, and function of planarian mechanosensory neurons. The authors provide solid evidence provided by gene expression and functional studies to demonstrate that POU4-2 is required for the maintenance and regeneration of functional mechanosensory neurons in planarians. Furthermore, the authors identify conserved genes associated with human auditory and rheosensory neurons as potential targets of this transcription factor.
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Reviewer #1 (Public review):
Summary:
In this manuscript, the authors explore the role of the conserved transcription factor POU4-2 in planarian maintenance and regeneration of mechanosensory neurons. The authors explore the role of this transcription factor and identify potential targets of this transcription factor. Importantly, many genes discovered in this work are deeply conserved, with roles in mechanosensation and hearing, indicating that planarians may be a useful model with which to study the roles of these key molecules. This work is important within the field of regenerative neurobiology, but also impactful for those studying the evolution of the machinery that is important for human hearing.
Strengths:
The paper is rigorous and thorough, with convincing support for the conclusions of the work.
Weaknesses:
Weaknesses are …
Reviewer #1 (Public review):
Summary:
In this manuscript, the authors explore the role of the conserved transcription factor POU4-2 in planarian maintenance and regeneration of mechanosensory neurons. The authors explore the role of this transcription factor and identify potential targets of this transcription factor. Importantly, many genes discovered in this work are deeply conserved, with roles in mechanosensation and hearing, indicating that planarians may be a useful model with which to study the roles of these key molecules. This work is important within the field of regenerative neurobiology, but also impactful for those studying the evolution of the machinery that is important for human hearing.
Strengths:
The paper is rigorous and thorough, with convincing support for the conclusions of the work.
Weaknesses:
Weaknesses are relatively minor and could be addressed with additional experiments or changes in writing.
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Reviewer #2 (Public review):
Summary:
In this manuscript, the authors investigate the role of the transcription factor Smed-pou4-2 in the maintenance, regeneration, and function of mechanosensory neurons in the freshwater planarian Schmidtea mediterranea. First, they characterize the expression of pou4-2 in mechanosensory neurons during both homeostasis and regeneration, and examine how its expression is affected by the knockdown of soxB1, 2, a previously identified transcription factor essential for the maintenance and regeneration of these neurons. Second, the authors assess whether pou4-2 is functionally required for the maintenance and regeneration of mechanosensory neurons.
Strengths:
The study provides some new insights into the regulatory role of pou4-2 in the differentiation, maintenance, and regeneration of ciliated …
Reviewer #2 (Public review):
Summary:
In this manuscript, the authors investigate the role of the transcription factor Smed-pou4-2 in the maintenance, regeneration, and function of mechanosensory neurons in the freshwater planarian Schmidtea mediterranea. First, they characterize the expression of pou4-2 in mechanosensory neurons during both homeostasis and regeneration, and examine how its expression is affected by the knockdown of soxB1, 2, a previously identified transcription factor essential for the maintenance and regeneration of these neurons. Second, the authors assess whether pou4-2 is functionally required for the maintenance and regeneration of mechanosensory neurons.
Strengths:
The study provides some new insights into the regulatory role of pou4-2 in the differentiation, maintenance, and regeneration of ciliated mechanosensory neurons in planarians.
Weaknesses:
The overall scope is relatively limited. The manuscript lacks clear organization, and many of the conclusions would benefit from additional experiments and more rigorous quantification to enhance their strength and impact.
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Author response:
(1) We will clarify statements comparing regeneration and developmental processes. Additionally, we will include a new supplemental figure with published data showing that the pou4-2 clone dd_Smed_v6_30562_0_1 (cross-referenced as SMED30002016) is expressed during stages corresponding to organ development in Schmidtea mediterranea (https://planosphere.stowers.org/feature/Schmidtea/mediterranea-sexual/transcript/SMED30002016).
(2) We will reorganize the figures by combining Figures 3 and 4 for improved clarity.
(3) We will address experimental and interpretive concerns regarding the role of atonal in the pou4-2 gene regulatory network.
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