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1.
Science ; 362(6417): 949-952, 2018 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-30467170

RESUMO

The emergence of asymmetry from an initially symmetrical state is a universal transition in nature. Living organisms show asymmetries at the molecular, cellular, tissular, and organismal level. However, whether and how multilevel asymmetries are related remains unclear. In this study, we show that Drosophila myosin 1D (Myo1D) and myosin 1C (Myo1C) are sufficient to generate de novo directional twisting of cells, single organs, or the whole body in opposite directions. Directionality lies in the myosins' motor domain and is swappable between Myo1D and Myo1C. In addition, Myo1D drives gliding of actin filaments in circular, counterclockwise paths in vitro. Altogether, our results reveal the molecular motor Myo1D as a chiral determinant that is sufficient to break symmetry at all biological scales through chiral interaction with the actin cytoskeleton.


Assuntos
Citoesqueleto de Actina/química , Proteínas de Drosophila/química , Modelos Moleculares , Miosina Tipo I/química , Animais , Proteínas de Drosophila/antagonistas & inibidores , Drosophila melanogaster/crescimento & desenvolvimento , Isomerismo , Larva , Miosina Tipo I/antagonistas & inibidores , Miosina Tipo V/química , Domínios Proteicos
2.
Diabetes Obes Metab ; 16 Suppl 1: 16-20, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25200291

RESUMO

Insulin and insulin-like growth factors (IGFs) are important regulators of growth and metabolism. In both vertebrates and invertebrates, insulin/IGFs are made available to various organs, including the brain, through two routes: the circulating systemic insulin/IGFs act on distant organs via endocrine signalling, whereas insulin/IGF ligands released by local tissues act in a paracrine or autocrine fashion. Although the mechanisms governing the secretion and action of systemic insulin/IGF have been the focus of extensive investigation, the significance of locally derived insulin/IGF has only more recently come to the fore. Local insulin/IGF signalling is particularly important for the development and homeostasis of the central nervous system, which is insulated from the systemic environment by the blood-brain barrier. Local insulin/IGF signalling from glial cells, the blood-brain barrier and the cerebrospinal fluid has emerged as a potent regulator of neurogenesis. This review will address the main sources of local insulin/IGF and how they affect neurogenesis during development. In addition, we describe how local insulin/IGF signalling couples neural stem cell proliferation with systemic energy state in Drosophila and in mammals.


Assuntos
Retroalimentação Fisiológica , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/metabolismo , Modelos Neurológicos , Neurogênese , Transdução de Sinais , Animais , Antígenos CD/metabolismo , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/metabolismo , Homeostase , Humanos , Secreção de Insulina , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Receptor IGF Tipo 1/agonistas , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/agonistas , Receptor de Insulina/metabolismo
3.
Semin Cell Dev Biol ; 19(3): 252-62, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18328746

RESUMO

Seminal studies of left-right (L/R) patterning in vertebrate models have led to the discovery of roles for the nodal pathway, ion flows and cilia in this process. Although the molecular mechanisms underlying L/R asymmetries seen in protostomes are less well understood, recent work using Drosophila melanogaster as a novel genetic model system to study this process has identified a number of mutations affecting directional organ looping. The genetic analysis of this, the most evolutionary conserved feature of L/R patterning, revealed the existence of a L/R pathway that involves the actin cytoskeleton and an associated type I myosin. In this review, we describe this work in the context of Drosophila development, and discuss the implications of these results for our understanding of L/R patterning in general.


Assuntos
Padronização Corporal , Drosophila melanogaster/embriologia , Animais , Biomarcadores/metabolismo , Mutação/genética
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