Hectd1 is required for development of the junctional zone of the placenta

Sarkar, Anjali A.; Nuwayhid, Samar; Maynard, Thomas M.; Ghandchi, Frederick; Hill, John E.; LaMantia, Anthony‐Samuel; Zohn, Irene E.

doi:10.1016/j.ydbio.2014.05.007

Cited by 33 publications

(33 citation statements)

References 55 publications

(89 reference statements)

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“…The severe placental defects described here and in our previous study [2] likely contribute to midgestation lethality and IUGR observed in Hectd1 mutants. Other developmental defects in Hectd1 mutants may also play a role such as complex cardiac defects [20], which could exacerbate or even cause placental defects.…”

Section: Discussionsupporting

confidence: 69%

“…Data presented here and in our previous study demonstrate that Hectd1 is essential for development of the murine placenta [19]. Hectd1 is expressed throughout development of this organ and enriched in some labyrinthine trophoblast populations including SynT-I and S-TGC cells [2].…”

Section: Discussionmentioning

confidence: 58%

“…Mutant placentas are smaller with defects in the junctional zone including decreased TGCs, spongiotrophoblasts and glycogen trophoblasts [2]. Mutant placentas also show increased numbers of immature uterine natural killer (uNK) cells in the maternal decidua [2]. Here we describe in detail defects in development of the labyrinthine zone.…”

Section: Discussionmentioning

confidence: 94%

“…Hectd1 is expressed throughout development of this organ and enriched in some labyrinthine trophoblast populations including SynT-I and S-TGC cells [2]. Mutant placentas are smaller with defects in the junctional zone including decreased TGCs, spongiotrophoblasts and glycogen trophoblasts [2]. Mutant placentas also show increased numbers of immature uterine natural killer (uNK) cells in the maternal decidua [2].…”

Section: Discussionmentioning

confidence: 99%

“…Hectd1 mutant embryos are smaller, show evidence of IUGR and die at mid-gestation [2]. Hectd1 opm/opm mutant placentas are smaller than wildtype littermates and show significant defects in development of the junctional zone [2]. Specifically, mutant placentas have reduced numbers of TGCs, glycogen trophoblasts, uterine natural killer cells (uNKs) and spongiotrophoblasts.…”

Section: Introductionmentioning

confidence: 99%

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Abnormal labyrinthine zone in the Hectd1 -null placenta

et al. 2016

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Introduction The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. Methods The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. Results Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). Discussion Together these defects indicate that Hectd1 is required for development of the labyrinthine zone or the mouse placenta.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Abnormal labyrinthine zone in the Hectd1 -null placenta

et al. 2016

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HECTD1‐Mediated Ubiquitination and Degradation of Rubicon Regulates Autophagy and Osteoarthritis Pathogenesis

Liao

Zheng

Shen

et al. 2023

Arthritis & Rheumatology

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Objective Osteoarthritis (OA) is one of the most common degenerative joint diseases and is associated with autophagy suppression. However, the molecular mechanism of autophagy regulation in the context of OA is not fully understood. In this study, we sought to determine the role that HECTD1 plays in the pathogenesis of OA. Methods We used RNA sequencing analysis to explore the differential expression of E3 ubiquitin ligase genes in healthy human cartilage and human cartilage affected by OA. Using surgery‐ and aging‐induced OA mouse models, we comprehensively analyzed the function of the screened gene Hectd1 in the development of OA; furthermore, we dissected the mechanism by which HECTD1 regulates autophagy and OA progression using a combination of molecular biologic, cell biologic, and biochemical approaches. Results HECTD1 was significantly down‐regulated in human OA cartilage samples compared to healthy cartilage samples. Overexpression of HECTD1 in mouse joints alleviated OA pathogenesis, whereas conditional depletion of Hectd1 in cartilage samples aggravated surgery‐ and aging‐induced OA pathogenesis. Mechanistically, HECTD1 bound to Rubicon and ubiquitinated Rubicon at lysine residue 534, which targets Rubicon for proteasomal degradation. More importantly, HECTD1‐mediated Rubicon degradation regulated chondrocyte autophagy, leading to mitigation of stress‐induced chondrocyte death and the subsequent progression of OA. Conclusion HECTD1 plays a crucial role in the pathogenesis of OA, in that HECTD1 regulates chondrocyte autophagy by ubiquitinating and targeting Rubicon for proteasomal degradation.

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