RESUMEN
BACKGROUND: Primary cilia are sensory organelles crucial for organ development. The pivotal structure of the primary cilia is a microtubule that is generated via tubulin polymerization reaction that occurs in the basal body. It remains to be elucidated how molecules with distinct physicochemical properties contribute to the formation of the primary cilia. RESULTS: Here we show that brain expressed X-linked 1 (Bex1) plays an essential role in tubulin polymerization and primary cilia formation. The Bex1 protein shows the physicochemical property of being an intrinsically disordered protein (IDP). Bex1 shows cell density-dependent accumulation as a condensate either in nucleoli at a low cell density or at the apical cell surface at a high cell density. The apical Bex1 localizes to the basal body. Bex1 knockout mice present ciliopathy phenotypes and exhibit ciliary defects in the retina and striatum. Bex1 recombinant protein shows binding capacity to guanosine triphosphate (GTP) and forms the condensate that facilitates tubulin polymerization in the reconstituted system. CONCLUSIONS: Our data reveals that Bex1 plays an essential role for the primary cilia formation through providing the reaction field for the tubulin polymerization.
Asunto(s)
Cilios , Proteínas del Tejido Nervioso/metabolismo , Tubulina (Proteína) , Animales , Condensados Biomoleculares , Cilios/metabolismo , Ratones , Ratones Noqueados , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismoRESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a lack of behavioral flexibility and stereotyped language. Food selectivity is common among children with ASD because of their persnickety nature. A prolonged unbalanced diet results in an increased risk of several diseases, such as iron deficiency anemia, scurvy, rickets, dry eye, and Wernicke encephalopathy. However, no cases of megaloblastic anemia have been reported to date. We report the case of an 11-year-old boy with ASD who developed megaloblastic anemia due to vitamin B12 deficiency. He had a prolonged history of selective eating for more than 10 years. His nutritional status on admission was poor, and he had low weight and short stature. His food selectivity was so strong that intervention to expand diet variety was unsuccessful. A developmental-behavioral pediatrician found that the patient had visual dominance and could take some medications when suffering from a minor illness. Nutritional supplements were selected after consultation with a nutritionist. Although compulsory treatment was necessary during the acute phase, the therapy was continued at home. With multidisciplinary intervention tailored to the patient and his parents' characteristics, his nutritional status improved in a few months.
Asunto(s)
Anemia Megaloblástica , Trastorno del Espectro Autista , Deficiencia de Vitamina B 12 , Humanos , Masculino , Niño , Anemia Megaloblástica/etiología , Trastorno del Espectro Autista/complicaciones , Deficiencia de Vitamina B 12/complicaciones , Dieta , Suplementos DietéticosRESUMEN
Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes that presents with uncontrolled hyperglycemia during the first 6 months of life. NDM is a rare disease in which gene variants mainly cause ß-cell loss or dysfunction (6q24 duplication, KCNJ11, and ABCC8). Although NDM is primarily treated through insulin therapy, it is highly challenging to manage blood glucose levels using insulin therapy during infancy. In contrast, KCNJ11 and ABCC8 mutant patients received oral sulfonylureas (SU) instead of insulin injections; however, the dose and frequency differ among individuals. Continuous glucose monitoring (CGM) is useful in patients with type 1 diabetes; but reports on patients with NDM are lacking. Herein, we report two cases of NDM with the KCNJ11 variant. We used CGM not only during insulin injection therapy but also after switching to oral SU therapy. The CGM data can also be used to determine the dose and frequency of SU. Furthermore, long-term CGM may be useful for adjusting SU dose and frequency, and maintaining good glycemic control not only during insulin injection but also during oral SU therapy.
RESUMEN
Epidermolysis bullosa (EB) is a group of inherited mechanobullous skin disease. The dystrophic EB (DEB), one subtype of EB, is inherited in an autosomal dominant DEB or in an autosomal recessive (RDEB). DEB is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. Over 300 pathogenic mutations have been detected within COL7A in DEB. Patients with the Hallopeau-Siemens type (HS-RDEB), most severe form of DEB, frequently have premature termination codon (PTC) mutations on both alleles. PTC mutations on both alleles result in depleted mRNA and α1 helix, and failure to form the triple helix structure characteristic of type VII collagen. As patients with HS-RDEB usually have a pair of heterozygous PTC mutations, there have been rarely reported homozygous ones in HS-RDEB. We report the first case of HS-RDEB homozygous PTC mutations of 5818delC in both COL7A1 alleles. This case report suggests the positional effect of PTC mutations and vigilance against early infantile death in EB including HS-RDEB.
Asunto(s)
Colágeno Tipo VII/genética , Epidermólisis Ampollosa Distrófica/genética , Mutación , ARN Mensajero/genética , Alelos , Colágeno Tipo VII/metabolismo , Análisis Mutacional de ADN , Epidermólisis Ampollosa Distrófica/metabolismo , Epidermólisis Ampollosa Distrófica/patología , Femenino , Genes Recesivos , Homocigoto , Humanos , Recién Nacido , Linaje , Fenotipo , Piel/patologíaRESUMEN
Cell competition is a cell-cell interaction mechanism which maintains tissue homeostasis through selective elimination of unfit cells. During early brain development, cells are eliminated through apoptosis. How cells are selected to undergo elimination remains unclear. Here we aimed to identify a role for cell competition in the elimination of suboptimal cells using an in vitro neuroepithelial model. Cell competition was observed when neural progenitor HypoE-N1 cells expressing RASV12 were surrounded by normal cells in the co-culture. The elimination through apoptosis was observed by cellular changes of RASV12 cells with rounding/fragmented morphology, by SYTOX blue-positivity, and by expression of apoptotic markers active caspase-3 and cleaved PARP. In this model, expression of juvenility-associated genes Srsf7 and Ezh2 were suppressed under cell-competitive conditions. Srsf7 depletion led to loss of cellular juvenescence characterized by suppression of Ezh2, cell growth impairment and enhancement of senescence-associated proteins. The cell bodies of eliminated cells were engulfed by the surrounding cells through phagocytosis. Our data indicates that neuroepithelial cell competition may have an important role for maintaining homeostasis in the neuroepithelium by eliminating suboptimal cells through loss of cellular juvenescence.