A comparative perspective on lung and gill regeneration

Abstract

The ability to continuously grow and regenerate the gills throughout life is a remarkable property of fish and amphibians. Considering that gill regeneration was first described over one century ago, it is surprising that the underlying mechanisms of cell and tissue replacement in the gills remain poorly understood. By contrast, the mammalian lung is a largely quiescent organ in adults but is capable of facultative regeneration following injury. In the course of the past decade, it has been recognized that lungs contain a population of stem or progenitor cells with an extensive ability to restore tissue; however, despite recent advances in regenerative biology of the lung, the signaling pathways that underlie regeneration are poorly understood. In this Review, we discuss the common evolutionary and embryological origins shared by gills and mammalian lungs. These are evident in homologies in tissue structure, cell populations, cellular function and genetic pathways. An integration of the literature on gill and lung regeneration in vertebrates is presented using a comparative approach in order to outline the challenges that remain in these areas, and to highlight the importance of using aquatic vertebrates as model organisms. The study of gill regeneration in fish and amphibians, which have a high regenerative potential and for which genetic tools are widely available, represents a unique opportunity to uncover common signaling mechanisms that may be important for regeneration of respiratory organs in all vertebrates. This may lead to new advances in tissue repair following lung disease.

Integrative biology of injury in animals

“…External respiratory structures, such as gills, are particularly prone to damage, but many animals can regenerate these structures [e.g. annelids, damselflies, fish, amphibians (Bely & Sikes, 2010 ; Brown & Emlet, 2020 ; Cadiz & Jonz, 2020 ; Drewes & Zoran, 1989 ; Eycleshvmer, 1906 ; Mierzwa et al ., 2020 ; Robinson et al ., 1991 b ; Saito et al ., 2019 ; Wells, 1952 )]. Siphons, which are used for pumping external water to the gills in bivalves and thus are important in respiratory function, can also often be regenerated (de Vlas, 1985 ; Meyer & Byers, 2005 ; Tomiyama, 2016 ).…”

Shifting the focus of zebrafish toward a model of the tumor microenvironment

“…Despite these differences, the zebrafish equivalent of these structures still has the potential to provide immense insight into tumor-TME interactions. The gills like lungs are sites of oxygen exchange and contain many of the same cell types, including alveolar epithelial type I cells (called pavement cells in fish), goblet cells, and neuroepithelial cells ( Cadiz and Jonz, 2020 ). Both lungs and gills are also important sites of barrier immunity where zebrafish have been used to study the developmental origins of tissue-resident macrophages ( Lin et al, 2020 ) and also gill/lung regeneration ( Cadiz and Jonz, 2020 ).…”

“…The gills like lungs are sites of oxygen exchange and contain many of the same cell types, including alveolar epithelial type I cells (called pavement cells in fish), goblet cells, and neuroepithelial cells ( Cadiz and Jonz, 2020 ). Both lungs and gills are also important sites of barrier immunity where zebrafish have been used to study the developmental origins of tissue-resident macrophages ( Lin et al, 2020 ) and also gill/lung regeneration ( Cadiz and Jonz, 2020 ). Furthermore, the zebrafish has become a well-established model to investigate lymphangiogenesis and the HSC niche ( Flores et al, 2010 ; Wattrus and Zon, 2018 ).…”

Dynamics of repair and regeneration of adult zebrafish respiratory gill tissue after cryoinjury.

“…Although they do not possess lungs, several studies including our own, have recently highlighted the potential of the adult zebrafish (Danio rerio) as an alternative model system for respiratory tissue investigations of inflammation and repair [9][10][11][12]. In the adult zebrafish, the respiratory organs are the gills which are located in branchial chambers on each side of the head under the protection of a bony flap, the operculum.…”

“…They found that resected filaments are 50% complete after ~ 40 days and 85% complete after ~160 days. The mechanism of gill filament regeneration after resection is believed to involve the formation of a blastema [12]. While very informative, this injury model could be further enhanced by studies that recapitulate the extensive tissue damage seen in chronic lung diseases.…”