0000000000033428
AUTHOR
Vicente Herranz Pérez
Centrioles Shape ERK Signaling Outcomes to Support Lung Branching
Centrioles comprise the heart of centrosomes, where they organize microtubules. To study the function of centrioles in development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from endoderm did not disrupt intestinal growth or development. In contrast, in the lung, loss of centrioles blocked branching. In lung, loss of centrioles led to apoptosis specifically of SOX2-expressing airway epithelial cells. Loss of centrioles also activated p53. Deleting p53 in mice with acentriolar endoderm rescued SOX2+ cell survival, lung branching and viability. To investigate why endoderm-wide p53 activation specifically disrupted SOX2+ cell survival,…
Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for b-MSH and desacetyl a-MSH in energy homeostasis
Objective: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated. Methods: We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived fro…
Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis
Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar material 1 (PCM1). To study the requirement for centriolar satellites, we generated mice lacking PCM1, a crucial component of satellites. Pcm1−/− mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia, and cerebellar hypoplasia, and variably expressive phenotypes such as hydronephrosis. As many of these phenotypes have been observed in human ciliopathies and satellites are implicated in cilia biology, we investigated whether cilia were affected. PCM1 was dispensable for ciliogenesis in many cell types, whereas Pcm1−/− multiciliated…
Human POMC processing in vitro and in vivo revealed by quantitative peptidomics
ABSTRACTHuman obesity can result from the aberrant production or processing of proopiomelanocortin (POMC) in hypothalamic neurons, but it is unclear which human POMC-derived peptides are most relevant to body weight regulation. To address this question, we analysed both hypothalamic neurons derived from human pluripotent stem cells (hPSCs) and primary human hypothalamic tissue using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS). In both in vitro- and in vivo-derived samples, we found that POMC was processed into β-melanocyte stimulating hormone (β-MSH), whose existence in the human brain has been controversial. β-MSH and desacetyl α-MSH (d-α-MSH) were produced at ro…
Caracterización de la familia génica LGI
158 pages.