PHRED-1 is a divergent neurexin-1 homolog that organizes muscle fibers and patterns organs during regeneration

Adler, Carolyn E.; Alvarado, Alejandro Sánchez

doi:10.1016/j.ydbio.2017.04.012

Cited by 16 publications

(14 citation statements)

References 53 publications

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“…2e–g ; Extended Data Fig. 6a ; 26 ). Taken together, we conclude that myoD and longitudinal muscle fibers are required for the regenerative response.…”

mentioning

confidence: 94%

Orthogonal muscle fibres have different instructive roles in planarian regeneration

Scimone

Cote

Reddien

2017

Nature

126

185

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The ability to regenerate missing body parts exists throughout the animal kingdom. Positional information is critical for regeneration, but how it is harbored and utilized by differentiated tissues is poorly understood. In planarians, positional information has been identified through RNA interference (RNAi) phenotypes in which the wrong tissues are regenerated. For example, Wnt pathway inhibition leads to regeneration of heads in place of tails1–3. Characterization of such striking adult phenotypes led to identification of genes expressed in a constitutive and regional manner, associated with patterning, called position control genes (PCGs). Most PCGs are expressed within the planarian muscle4. Despite this major positional information role for muscle in planarians, how muscle is specified and how different muscle subsets impact regeneration is unknown. Here we found distinct regulatory roles for different planarian muscle fibers during regeneration. myoD was required for formation of a specific muscle cell subset: the longitudinal fibers, oriented along the anterior-posterior (AP) axis. Loss of longitudinal fibers led to a complete regeneration failure because of defects in regeneration initiation. A different transcription factor (TF)-encoding gene, nkx1-1, was required for formation of circular fibers, oriented along the medial-lateral (ML) axis. Loss of circular fibers led to a bifurcated AP axis with fused heads forming in single anterior blastemas. Our results demonstrate distinct roles for muscle fiber types in orchestrating planarian regeneration. Whereas muscle is often viewed as a strictly contractile tissue, these findings reveal specific regulatory roles for distinct muscle classes in wound signaling and patterning to enable regeneration.

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“…2e–g ; Extended Data Fig. 6a ; 26 ). Taken together, we conclude that myoD and longitudinal muscle fibers are required for the regenerative response.…”

mentioning

confidence: 94%

Orthogonal muscle fibres have different instructive roles in planarian regeneration

Scimone

Cote

Reddien

2017

Nature

126

185

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“…Growth and regeneration of intestinal branches require considerable remodeling of pre-existing tissue (19). Remodeling is governed by axial polarity cues (16, 20), ERK and EGFR signaling pathways (21–23), cytoskeletal regulators (24), and interactions with muscle (25–28). However, the mechanisms by which post-mitotic intestinal cells sense and respond to extrinsic signals are only superficially understood.…”

Section: Introductionmentioning

confidence: 99%

Cell-type diversity and regionalized gene expression in the planarian intestine revealed by laser-capture microdissection transcriptome profiling

Forsthoefel

Cejda

Khan

et al. 2019

Preprint

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Organ regeneration requires precise coordination of new cell differentiation and remodeling of uninjured tissue to faithfully re-establish organ morphology and function. An atlas of gene expression and cell types in the uninjured state is therefore an essential pre-requisite for understanding how damage is repaired. Here, we use laser-capture microdissection (LCM) and RNA-Seq to define the transcriptome of the intestine of Schmidtea mediterranea, a planarian flatworm with exceptional regenerative capacity. Bioinformatic analysis of 1,844 intestine-enriched transcripts suggests extensive conservation of digestive physiology with other animals, including humans. Comparison of the intestinal transcriptome to purified absorptive intestinal cell (phagocyte) and published single-cell expression profiles confirms the identities of known intestinal cell types, and also identifies hundreds of additional transcripts with previously undetected intestinal enrichment. Furthermore, by assessing the expression patterns of 143 transcripts in situ, we discover unappreciated mediolateral regionalization of gene expression and cell-type diversity, especially among goblet cells. Demonstrating the utility of the intestinal transcriptome, we identify 22 intestine-enriched transcription factors, and find that several have distinct functional roles in the regeneration and maintenance of goblet cells. Furthermore, depletion of goblet cells inhibits planarian feeding and reduces viability. Altogether, our results show that LCM is a viable approach for assessing tissue-specific gene expression in planarians, and provide a new resource for further investigation of digestive tract regeneration, the physiological roles of intestinal cell types, and axial polarity.

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“…Transducin, a G Protein heterotrimer, was the first structurally characterized WD40 protein whose beta-subunit interacts with both alpha and gamma subunit through a WD40 domain 6 – 10 . Just as beta subunit of heterotrimeric G-protein, all WD40 proteins provide platform to assemble proteins, DNA or RNA into functional complexes 1 , 11 , involving in DNA replication 12 – 15 , nucleosome assembly 16 , transcription 17 , RNA processing 18 , 19 , histone modification 20 – 24 , protein degradation 21 , 25 – 28 and other processes 5 , 29 – 31 .…”

Section: Introductionmentioning

confidence: 99%

Biophysical and structural characterization of the thermostable WD40 domain of a prokaryotic protein, Thermomonospora curvata PkwA

Shen

Qiao

et al. 2018

Sci Rep

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WD40 proteins belong to a big protein family with members identified in every eukaryotic proteome. However, WD40 proteins were only reported in a few prokaryotic proteomes. Using WDSP (http://wu.scbb.pkusz.edu.cn/wdsp/), a prediction tool, we identified thousands of prokaryotic WD40 proteins, among which few proteins have been biochemically characterized. As shown in our previous bioinformatics study, a large proportion of prokaryotic WD40 proteins have higher intramolecular sequence identity among repeats and more hydrogen networks, which may indicate better stability than eukaryotic WD40s. Here we report our biophysical and structural study on the WD40 domain of PkwA from Thermomonospora curvata (referred as tPkwA-C). We demonstrated that the stability of thermophilic tPkwA-C correlated to ionic strength and tPkwA-C exhibited fully reversible unfolding under different denaturing conditions. Therefore, the folding kinetics was also studied through stopped-flow circular dichroism spectra. The crystal structure of tPkwA-C was further resolved and shed light on the key factors that stabilize its beta-propeller structure. Like other WD40 proteins, DHSW tetrad has a significant impact on the stability of tPkwA-C. Considering its unique features, we proposed that tPkwA-C should be a great structural template for protein engineering to study key residues involved in protein-protein interaction of a WD40 protein.

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PHRED-1 is a divergent neurexin-1 homolog that organizes muscle fibers and patterns organs during regeneration

Cited by 16 publications

References 53 publications

Orthogonal muscle fibres have different instructive roles in planarian regeneration

Orthogonal muscle fibres have different instructive roles in planarian regeneration

Cell-type diversity and regionalized gene expression in the planarian intestine revealed by laser-capture microdissection transcriptome profiling

Biophysical and structural characterization of the thermostable WD40 domain of a prokaryotic protein, Thermomonospora curvata PkwA

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