Anna D'Angelo - Academia.edu (original) (raw)
Papers by Anna D'Angelo
PathoGenetics, 2009
Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. ... more Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity.
PLoS ONE, 2012
Oral-facial-digital type I syndrome (OFDI) is a human X-linked dominant-male-lethal developmental... more Oral-facial-digital type I syndrome (OFDI) is a human X-linked dominant-male-lethal developmental disorder caused by mutations in the OFD1 gene. Similar to other inherited disorders associated to ciliary dysfunction OFD type I patients display neurological abnormalities. We characterized the neuronal phenotype that results from Ofd1 inactivation in early phases of mouse embryonic development and at post-natal stages. We determined that Ofd1 plays a crucial role in forebrain development, and in particular, in the control of dorso-ventral patterning and early corticogenesis. We observed abnormal activation of Sonic hedgehog (Shh), a major pathway modulating brain development. Ultrastructural studies demonstrated that early Ofd1 inactivation results in the absence of ciliary axonemes despite the presence of mature basal bodies that are correctly orientated and docked. Ofd1 inducible-mediated inactivation at birth does not affect ciliogenesis in the cortex, suggesting a developmental stage-dependent role for a basal body protein in ciliogenesis. Moreover, we showed defects in cytoskeletal organization and apical-basal polarity in Ofd1 mutant embryos, most likely due to lack of ciliary axonemes. Thus, the present study identifies Ofd1 as a developmental disease gene that is critical for forebrain development and ciliogenesis in embryonic life, and indicates that Ofd1 functions after docking and before elaboration of the axoneme in vivo.
Pediatric Nephrology, 2010
Primary cilia are specialized organelles consisting of an axoneme anchored to the plasma membrane... more Primary cilia are specialized organelles consisting of an axoneme anchored to the plasma membrane through the basal body consisting of two centrioles. They protrude from the cell surface of almost all mammalian cells. Mutations in genes encoding for ciliary proteins cause ciliopathies, which are characterized by a wide spectrum of phenotypes, including polycystic kidney, hepatic disease, malformations in the central nervous system, skeletal defects, retinal degeneration, and obesity. Both clinical studies and animal models have revealed that during embryogenesis, primary cilium play an essential role in defining the correct patterning of the body. In this study, we focused our attention on the tissues mainly affected in ciliopathies, such as the kidney, liver, and central nervous system. Emerging studies reveal that the primary cilium may play similar roles, leading to distinct functions according to the different cell type and developmental stages. The state of the art in primary cilia studies reveals a very complex role. The aim of this review is to evaluate the recent advances in the function of primary cilia in different tissues, underlining similarities and differences.
Additional file 1. Composition of transport and culture media used for bovine respiratory explants.
PathoGenetics, 2009
Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. ... more Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity.
PLoS ONE, 2012
Oral-facial-digital type I syndrome (OFDI) is a human X-linked dominant-male-lethal developmental... more Oral-facial-digital type I syndrome (OFDI) is a human X-linked dominant-male-lethal developmental disorder caused by mutations in the OFD1 gene. Similar to other inherited disorders associated to ciliary dysfunction OFD type I patients display neurological abnormalities. We characterized the neuronal phenotype that results from Ofd1 inactivation in early phases of mouse embryonic development and at post-natal stages. We determined that Ofd1 plays a crucial role in forebrain development, and in particular, in the control of dorso-ventral patterning and early corticogenesis. We observed abnormal activation of Sonic hedgehog (Shh), a major pathway modulating brain development. Ultrastructural studies demonstrated that early Ofd1 inactivation results in the absence of ciliary axonemes despite the presence of mature basal bodies that are correctly orientated and docked. Ofd1 inducible-mediated inactivation at birth does not affect ciliogenesis in the cortex, suggesting a developmental stage-dependent role for a basal body protein in ciliogenesis. Moreover, we showed defects in cytoskeletal organization and apical-basal polarity in Ofd1 mutant embryos, most likely due to lack of ciliary axonemes. Thus, the present study identifies Ofd1 as a developmental disease gene that is critical for forebrain development and ciliogenesis in embryonic life, and indicates that Ofd1 functions after docking and before elaboration of the axoneme in vivo.
Pediatric Nephrology, 2010
Primary cilia are specialized organelles consisting of an axoneme anchored to the plasma membrane... more Primary cilia are specialized organelles consisting of an axoneme anchored to the plasma membrane through the basal body consisting of two centrioles. They protrude from the cell surface of almost all mammalian cells. Mutations in genes encoding for ciliary proteins cause ciliopathies, which are characterized by a wide spectrum of phenotypes, including polycystic kidney, hepatic disease, malformations in the central nervous system, skeletal defects, retinal degeneration, and obesity. Both clinical studies and animal models have revealed that during embryogenesis, primary cilium play an essential role in defining the correct patterning of the body. In this study, we focused our attention on the tissues mainly affected in ciliopathies, such as the kidney, liver, and central nervous system. Emerging studies reveal that the primary cilium may play similar roles, leading to distinct functions according to the different cell type and developmental stages. The state of the art in primary cilia studies reveals a very complex role. The aim of this review is to evaluate the recent advances in the function of primary cilia in different tissues, underlining similarities and differences.
Additional file 1. Composition of transport and culture media used for bovine respiratory explants.