TY  - JOUR
AB  - Limb regeneration in salamanders is achieved by a complex coordination of various biological processes and requires the proper integration of new tissue with old. Among the tissues found inside the limb, the skeleton is the most prominent component, which serves as a scaffold and provides support for locomotion in the animal. Throughout the years, researchers have studied the regeneration of the appendicular skeleton in salamanders both after limb amputation and as a result of fracture healing. The final outcome has been widely seen as a faithful re-establishment of the skeletal elements, characterised by a seamless integration into the mature tissue. The process of skeletal integration, however, is not well understood, and several works have recently provided evidence of commonly occurring flawed regenerates. In this Review, we take the reader on a journey through the course of bone formation and regeneration in salamanders, laying down a foundation for critically examining the mechanisms behind skeletal integration. Integration is a phenomenon that could be influenced at various steps of regeneration, and hence, we assess the current knowledge in the field and discuss how early events, such as tissue histolysis and patterning, influence the faithful regeneration of the appendicular skeleton.
AU  - Riquelme-Guzmán, C.*
AU  - Sandoval-Guzmán, T.
C1  - 69956
C2  - 55337
CY  - Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
TI  - The salamander limb: A perfect model to understand imperfect integration during skeletal regeneration.
JO  - Biol. Open
VL  - 13
IS  - 2
PB  - Company Biologists Ltd
PY  - 2024
ER  - 

TY  - JOUR
AB  - EPCAM (Epithelial Cell Adhesion Molecule) is a transmembrane glycoprotein expressed on the surface of most epithelial and epithelium-derived tumor cells and reported to regulate stability of epithelial tight junction proteins, claudins. Despite its widespread expression, loss of EPCAM function has so far only been reported to prominently affect intestinal development, resulting in severe early onset enteropathy associated with impaired growth and decreased survival in both humans and mice. In this study, we show that the critical role of EPCAM is not limited to intestinal tissues and that it shares its essential function with its only known homolog, TROP2 (Trophoblast cell surface antigen 2). EPCAM-deficient mice show significant growth retardation and die within four weeks after birth. In addition to changes in small and large intestines, loss of EPCAM results in hyperkeratosis in skin and forestomach, hair follicle atrophy leading to alopecia, nephron hypoplasia in kidney, proteinuria, and altered production of digestive enzymes by pancreas. Expression of TROP2 partially, but not completely, overlaps with EPCAM in a number developing epithelia. Although loss of TROP2 had no gross impact on mouse development and survival, TROP2 deficiency generally compounded developmental defects observed in EPCAM-deficient mice, led to about 60% decrease in embryonic viability, and further shortened postnatal lifespan of born pups. Importantly, TROP2 was able to compensate for the loss of EPCAM in stabilizing claudin-7 expression and cell membrane localization in tissues that co-express both proteins. These findings identify overlapping functions of EPCAM and TROP2 as regulators of epithelial development in both intestinal and extraintestinal tissues.
AU  - Szabo, R.*
AU  - Ward, J.M.*
AU  - Artunc, F.
AU  - Bugge, T.H.*
C1  - 65544
C2  - 52726
TI  - EPCAM and TROP2 share role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice.
JO  - Biol. Open
VL  - 11
IS  - 7
PY  - 2022
ER  - 

TY  - JOUR
AB  - Animals have evolved two general strategies to counter injury and maintain physiological function. The most prevalent is protection by isolating vital organs into body cavities. However, protection is not optimal for sensory systems because their external components need to be exposed to the environment to fulfill their receptive function. Thus, a common strategy to maintain sensory abilities against persistent environmental insult involves repair and regeneration. However, whether age or frequent injuries affect the regenerative capacity of sensory organs remains unknown. We have found that neuromasts of the zebrafish lateral line regenerate mechanosensory hair cells after recurrent severe injuries and in adulthood. Moreover, neuromasts can reverse transient imbalances of Notch signaling that result in defective organ proportions during repair. Our results reveal inextinguishable hair-cell regeneration in the lateral line, and suggest that the neuromast epithelium is formed by plastic territories that are maintained by continuous intercellular communication.
AU  - Pinto-Teixeira, F.*
AU  - Viader Llargues, O.*
AU  - Torres-Mejia, E.*
AU  - Turan, M.*
AU  - Gonzalez-Gualda, E.*
AU  - Pola-Morell, L.*
AU  - López-Schier, H.
C1  - 46532
C2  - 37737
CY  - Cambridge
SP  - 903-909
TI  - Inexhaustible hair-cell regeneration in young and aged zebrafish.
JO  - Biol. Open
VL  - 4
IS  - 7
PB  - Company Of Biologists Ltd
PY  - 2015
ER  - 

TY  - JOUR
AB  - Parkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes linked with the onset of Parkinson's disease, DJ-1/PARK7, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson's related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson's disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson's disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson's disease.
AU  - Toyoda, Y.*
AU  - Erkut, C.*
AU  - Pan-Montojo, F.*
AU  - Boland, S.*
AU  - Stewart, M.P.*
AU  - Müller, D.J.*
AU  - Wurst, W.
AU  - Hyman, A.A.*
AU  - Kurzchalia, T.V.*
C1  - 31827
C2  - 34777
CY  - Cambridge
SP  - 777-784
TI  - Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival.
JO  - Biol. Open
VL  - 3
IS  - 8
PB  - Company Of Biologists Ltd
PY  - 2014
ER  -