Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet endocrine cell differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature and innervation, islet microenvironment, and ß cell mass, we transiently increased VEGF-A production by ß cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to ß cell loss. After withdrawal of the VEGF-A stimulus, ß cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing ß cells. Bone marrow-derived macrophages (MFs) recruited to the site of ß cell injury were crucial for the ß cell proliferation, which was independent of pancreatic location and circulating factors such as glucose. Identification of the signals responsible for the proliferation of adult, terminally differentiated ß cells will improve strategies aimed at ß cell regeneration and expansion. Overall design: Examination of RNA profiles from isolated whole islets from RIP-rtTA; TetO-VEGF-A mice with no doxycycline (Dox) treatment (3 samples) and after 1 week of Dox (3 sample); and islet-derived macrophages (3 samples) and endothelial cells (3 samples) isolated from dispersed purified islets from RIP-rtTA; TetO-VEGF-A mice after 1 week Dox treatment by fluorescence-activated cell sorting using antibodies against CD11b and CD31, respectively.
Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding.
Specimen part, Cell line, Treatment, Subject
View SamplesThe zebrafish pineal gland (epiphysis) is an autonomous clock organ. In addition to being a site of melatonin production, it contains photoreceptor cells and functions as a circadian clock pace maker, making zebrafish a useful model system to study the developmental control of expression of genes associated with melatonin synthesis and photodetection, and the circadian clock. Here we have used DNA microarray technology to study the zebrafish pineal transcriptome. Analysis of gene expression at five different developmental stages (three embryonic and two adult) has revealed a highly dynamic transcriptional profile, revealing many genes that are highly expressed in the pineal gland. Statistical analysis of the data based on Gene Ontology (GO) annotation indicates that many transcription factors and cell cycle genes are highly expressed during embryonic stages, whereas genes dedicated to visual system signal transduction are preferentially expressed in the adult. Furthermore, several genes were identified that exhibit day/night differences in expression. Our data provide a rich source of candidate genes for distinct functions at different stages of pineal gland development.
Transcriptome analysis of the zebrafish pineal gland.
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