<i>TBX2/3</i> is required for regeneration of dorsal‐ventral and medial‐lateral polarity in planarians

Tian, Qingnan; Sun, Ying; Gao, Tingting; Li, Jiaxin; Hao, Zhimin; Fang, Huiying; Zhang, Shoutao

doi:10.1002/jcb.29905

Cited by 6 publications

(7 citation statements)

References 51 publications

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“…Given these results, we next investigated potential regulation of wnt1 by other factors known to act with BMP signaling to control dorsoventral identity. We examined the effects of inhibiting tbx2/3 , a transcription factor hypothesized to act downstream of bmp4 for control of DV identity in Dugesia japonica (40). Following 18 days of tbx2/3 RNAi, wnt1 expression was likewise significantly expanded toward the anterior (Fig.…”

Section: Resultsmentioning

confidence: 99%

BMP suppresses WNT to integrate patterning of orthogonal body axes in adult planarians

Clark

Petersen

2023

Preprint

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Adult regeneration restores patterning of orthogonal body axes after damage in a postembryonic context. Planarians regenerate using distinct body-wide signals primarily regulating each axis dimension: anteroposterior Wnts, dorsoventral BMP, and mediolateral Wnt5 and Slit determinants. How regeneration can consistently form perpendicular tissue axes without symmetry-breaking embryonic events is unknown, and could either occur using fully independent, or alternatively, integrated signals defining each dimension. Here, we report that the planarian dorsoventral regulator bmp4 suppresses the posterior determinant wnt1 to pattern the anteroposterior axis. Double-FISH identified distinct anteroposterior domains within dorsal midline muscle that express either bmp4 or wnt1. Homeostatic inhibition bmp4 and smad1 expanded the wnt1 expression anteriorly, while elevation of BMP signaling through nog1;nog2 RNAi reduced the wnt1 expression domain. BMP signal perturbation broadly affected anteroposterior identity as measured by expression of posterior Wnt pathway factors, without affecting head regionalization. Therefore, dorsal BMP signals broadly limit posterior identity. Furthermore, bmp4 RNAi caused medial expansion of the lateral determinant wnt5 and reduced expression of the medial regulator slit. Double RNAi of bmp4 and wnt5 resulted in lateral ectopic eye phenotypes, suggesting bmp4 acts upstream of wnt5 to pattern the mediolateral axis. Therefore, bmp4 acts at the top of a patterning hierarchy both to control dorsoventral information and also, through suppression of Wnt signals, to regulate anteroposterior and mediolateral identity. These results reveal that adult pattern formation involves integration of signals controlling individual orthogonal axes.

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Section: Resultsmentioning

confidence: 99%

BMP suppresses WNT to integrate patterning of orthogonal body axes in adult planarians

Clark

Petersen

2023

Preprint

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“…All experiments were performed with the clonal strain of the planarian Dugesia japonica . Animals were kept at 20°C in autoclaved stream water as previously described 27 . Planarians 4–6 mm in length were starved for at least 1 week prior to experiments.…”

Section: Methodsmentioning

confidence: 99%

MRLC controls apoptotic cell death and functions to regulate epidermal development during planarian regeneration and homeostasis

et al. 2023

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Adult stem cells (ASCs) are pluripotent cells with the capacity to self‐renew and constantly replace lost cells due to physiological turnover or injury. Understanding the molecular mechanisms of the precise coordination of stem cell proliferation and proper cell fate decision is important to regeneration and organismal homeostasis. The planarian epidermis provides a highly tractable model to study ASC complex dynamic due to the distinct spatiotemporal differentiation stages during lineage development. Here, we identified the myosin regulatory light chain (MRLC) homologue in the Dugesia japonica transcriptome. We found high expression levels of MRLC in wound region during regeneration and also expressed in late epidermal progenitors as an essential regulator of the lineage from neoblasts to mature epidermal cells. We investigated the function of MRLC using in situ hybridization, real‐time polymerase chain reaction and double fluorescent and uncovered the potential mechanism. Knockdown of MRLC leads to a remarkable increase in cell death, causes severe abnormalities during regeneration and homeostasis and eventually leads to animal death. The global decrease in epidermal cell in MRLC RNAi animals induces accelerated epidermal proliferation and differentiation. Additionally, we find that MRLC is co‐expressed with cdc42 and acts cooperatively to control the epidermal lineage development by affecting cell death. Our results uncover an important role of MRLC, as an inhibitor of apoptosis, involves in epidermal development.

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“…Transcription factors (TFs) play key roles in multiple aspects of animal development. In planarians, many conserved TFs have been identified (Suzuki-Horiuchi et al, 2021) and characterized to be required for the regeneration of multiple cells, tissues and organs including the intestine (Flores et al, 2016; Forsthoefel et al, 2012; Forsthoefel et al, 2020; González-Sastre et al, 2017), the eyes (Lapan and Reddien, 2011; Lapan and Reddien, 2012; Mannini et al, 2004; Pineda et al, 2000), the central nervous system (Brown et al, 2018; Coronel-Córdoba et al, 2022; Cowles et al, 2013; Cowles et al, 2014; Currie and Pearson, 2013; Fraguas et al, 2014; März et al, 2013; Roberts-Galbraith et al, 2016; Ross et al, 2018), the epidermis (Dubey et al, 2022; Tu et al, 2015), the pharynx (Adler et al, 2014), the pigment cells (He et al, 2017; Wang et al, 2016), the musculature (Scimone et al, 2017; Scimone et al, 2018), the excretory system (Scimone et al, 2011), as well as for the establishment of axial polarity (Blassberg et al, 2013; Chen et al, 2013; Felix and Aboobaker, 2010; Hayashi et al, 2011; Pascual-Carreras et al, 2023; Scimone et al, 2014; Tian et al, 2021; Vásquez-Doorman and Petersen, 2014).…”

Section: Introductionmentioning

confidence: 99%

LIM-HD transcription factors are required for regeneration of neuronal and intestinal cell subtypes in planarians

Molina

Abduljabbar

Fraguas

et al. 2023

Preprint

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Adult planarians can regenerate the gut, eyes, and even a functional brain in just a few days after injury. Proper regeneration of these complex structures requires that signals guide and restrict the commitment of their adult stem cells and ensure the identity and patterning of the newly formed structures. During embryogenesis of both vertebrates and invertebrates, LIM Homeodomain (LIM-HD) transcription factors act in a combinatorial 'LIM code' that controls crucial aspects of cell fate determination and cell differentiation, including specification of neuronal cell type identity and axonal guidance. So far, however, our understanding about the role these genes may play during regeneration is limited. Here, we report the identification and functional characterization of the full repertoire of LIM-HD genes in Schmidtea mediterranea. We found that these lim homeobox genes (lhx) appear mainly expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian. By functional RNAi based analysis we have identified that several Smed-lhx genes (islet1, lhx1/5-1, lhx2/9-3, lhx6/8, lmx1a/b-2 and lmx1a/b-3) are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while others (Smed-lhx1/5.2 and Smed-lhx2/9.2) are required for the proper expression of diverse intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in the control of axonal pathfinding (lhx6/8), axial patterning (islet1 and lmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4, lhx2/9-3, lmx1a/b-2 and lmx1a/b-3) in planarians. Altogether, our results suggest that planarian LIM-HD could provide a combinatorial LIM code to control axial patterning, axonal growing as well as to specify distinct neuronal and intestinal cell identities during regeneration.

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TBX2/3 is required for regeneration of dorsal‐ventral and medial‐lateral polarity in planarians

Cited by 6 publications

References 51 publications

BMP suppresses WNT to integrate patterning of orthogonal body axes in adult planarians

BMP suppresses WNT to integrate patterning of orthogonal body axes in adult planarians

MRLC controls apoptotic cell death and functions to regulate epidermal development during planarian regeneration and homeostasis

LIM-HD transcription factors are required for regeneration of neuronal and intestinal cell subtypes in planarians

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