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1.
Development ; 144(18): 3278-3288, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28807896

RESUMO

Classical descriptions of the hypothalamus divide it into three rostro-caudal domains but little is known about their embryonic origins. To investigate this, we performed targeted fate-mapping, molecular characterisation and cell cycle analyses in the embryonic chick. Presumptive hypothalamic cells derive from the rostral diencephalic ventral midline, lie above the prechordal mesendoderm and express Fgf10Fgf10+ progenitors undergo anisotropic growth: those displaced rostrally differentiate into anterior cells, then those displaced caudally differentiate into mammillary cells. A stable population of Fgf10+ progenitors is retained within the tuberal domain; a subset of these gives rise to the tuberal infundibulum - the precursor of the posterior pituitary. Pharmacological approaches reveal that Shh signalling promotes the growth and differentiation of anterior progenitors, and also orchestrates the development of the infundibulum and Rathke's pouch - the precursor of the anterior pituitary. Together, our studies identify a hypothalamic progenitor population defined by Fgf10 and highlight a role for Shh signalling in the integrated development of the hypothalamus and pituitary.


Assuntos
Padronização Corporal , Diferenciação Celular , Fator 10 de Crescimento de Fibroblastos/metabolismo , Hipotálamo/citologia , Hipotálamo/embriologia , Células-Tronco/citologia , Animais , Anisotropia , Proliferação de Células , Embrião de Galinha , Galinhas , Diencéfalo/embriologia , Endoderma/embriologia , Proteínas Hedgehog/metabolismo , Mesoderma/embriologia , Modelos Biológicos , Sistemas Neurossecretores/metabolismo , Transdução de Sinais , Somitos/embriologia , Somitos/metabolismo , Células-Tronco/metabolismo , Regulação para Cima
2.
J Neuroendocrinol ; 31(5): e12727, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31050853

RESUMO

The adult hypothalamus is subdivided into distinct domains: pre-optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views of hypothalamic development, which traditionally have attempted to map adult domains to correspondingly located embryonic domains. Instead, new studies indicate that hypothalamic neurones arise from progenitor cells that undergo anisotropic growth, expanding to a greater extent than other progenitors, and grow in different dimensions. We describe in particular how a multipotent Shh/ Fgf10-expressing progenitor population gives rise to progenitors throughout the basal hypothalamus that grow anisotropically and sequentially: first, a subset displaced rostrally give rise to anterior-ventral/tuberal neuronal progenitors; then a subset displaced caudally give rise to mammillary neuronal progenitors; and, finally, a subset(s) displaced ventrally give rise to tuberal infundibular glial progenitors. As this occurs, stable populations of Shh+ive and Fgf10+ive progenitors form. We describe current understanding of the mechanisms that induce Shh+ive /Fgf10+ive progenitors and begin to direct their differentiation to anterior-ventral/tuberal neuronal progenitors, mammillary neuronal progenitors and tuberal infundibular progenitors. Taken together, these studies suggest a new model for hypothalamic development that we term the "anisotropic growth model". We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.


Assuntos
Hipotálamo/crescimento & desenvolvimento , Animais , Fator 10 de Crescimento de Fibroblastos/metabolismo , Proteínas Hedgehog/metabolismo , Humanos , Modelos Neurológicos , Células-Tronco Neurais/fisiologia , Neurônios/fisiologia
3.
Polymers (Basel) ; 11(5)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035360

RESUMO

Degradable polymers are crucial in order to reduce plastic environmental pollution and waste accumulation. In this paper, a natural product, tannic acid was modified to be used as a polymer star core. The tannic acid was modified with atom transfer radical polymerization (ATRP) initiators and characterized by 1H NMR, FT-IR, and XPS. Twenty-five arm polymer stars were prepared by photoinduced ATRP of poly(methyl methacrylate) (PMMA) or poly(oligo(ethylene oxide) methacrylate) (molar mass Mw = 300 g/mol) (P(OEO300MA)). The polymer stars were degraded by cleaving the polymer star arms attached to the core by phenolic esters under mild basic conditions. The stars were analyzed before and after degradation by gel permeation chromatography (GPC). Cytotoxicity assays were performed on the P(OEO300MA) stars and corresponding degraded polymers, and were found to be nontoxic at the concentrations tested.

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