The novel gene asb11: a regulator of the size of the neural progenitor compartment

Sander H. Diks; Robert J. Bink; Sandra van de Water; Jos Joore; Carina van Rooijen; Fons J. Verbeek; Jeroen den Hertog; Maikel P. Peppelenbosch; Danica Zivkovic

doi:10.1083/jcb.200601081

The novel gene asb11: a regulator of the size of the neural progenitor compartment

The Journal of Cell Biology ◽

10.1083/jcb.200601081 ◽

2006 ◽

Vol 174 (4) ◽

pp. 581-592 ◽

Cited By ~ 24

Author(s):

Sander H. Diks ◽

Robert J. Bink ◽

Sandra van de Water ◽

Jos Joore ◽

Carina van Rooijen ◽

...

Keyword(s):

Neuronal Differentiation ◽

Relative Increase ◽

Cytokine Signaling ◽

The Novel ◽

Suppressor Of Cytokine Signaling ◽

Neuronal Progenitor ◽

Undifferentiated State ◽

The Central Nervous System ◽

Progenitor Compartment ◽

Danio Rerio Embryos

From a differential display designed to isolate genes that are down-regulated upon differentiation of the central nervous system in Danio rerio embryos, we isolated d-asb11 (ankyrin repeat and suppressor of cytokine signaling box–containing protein 11). Knockdown of the d-Asb11 protein altered the expression of neural precursor genes sox2 and sox3 and resulted in an initial relative increase in proneural cell numbers. This was reflected by neurogenin1 expansion followed by premature neuronal differentiation, as demonstrated by HuC labeling and resulting in reduced size of the definitive neuronal compartment. Forced misexpression of d-asb11 was capable of ectopically inducing sox2 while it diminished or entirely abolished neurogenesis. Overexpression of d-Asb11 in both a pluripotent and a neural-committed progenitor cell line resulted in the stimulus-induced inhibition of terminal neuronal differentiation and enhanced proliferation. We conclude that d-Asb11 is a novel regulator of the neuronal progenitor compartment size by maintaining the neural precursors in the proliferating undifferentiated state possibly through the control of SoxB1 transcription factors.

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Hypothyroidism Compromises Hypothalamic Leptin Signaling in Mice

Molecular Endocrinology ◽

10.1210/me.2012-1311 ◽

2013 ◽

Vol 27 (4) ◽

pp. 586-597 ◽

Cited By ~ 16

Author(s):

Claudia Groba ◽

Steffen Mayerl ◽

Alies A. van Mullem ◽

Theo J. Visser ◽

Veerle M. Darras ◽

...

Keyword(s):

Arcuate Nucleus ◽

Leptin Receptor ◽

Cytokine Signaling ◽

Suppressor Of Cytokine Signaling ◽

Double Knockout ◽

Hypothalamic Arcuate Nucleus ◽

The Central Nervous System ◽

Leptin Expression ◽

The Impact

Abstract The impact of thyroid hormone (TH) on metabolism and energy expenditure is well established, but the role of TH in regulating nutritional sensing, particularly in the central nervous system, is only poorly defined. Here, we studied the consequences of hypothyroidism on leptin production as well as leptin sensing in congenital hypothyroid TRH receptor 1 knockout (Trhr1 ko) mice and euthyroid control animals. Hypothyroid mice exhibited decreased circulating leptin levels due to a decrease in fat mass and reduced leptin expression in white adipose tissue. In neurons of the hypothalamic arcuate nucleus, hypothyroid mice showed increased leptin receptor Ob-R expression and decreased suppressor of cytokine signaling 3 transcript levels. In order to monitor putative changes in central leptin sensing, we generated hypothyroid and leptin-deficient animals by crossing hypothyroid Trhr1 ko mice with the leptin-deficient ob/ob mice. Hypothyroid Trhr1/ob double knockout mice showed a blunted response to leptin treatment with respect to body weight and food intake and exhibited a decreased activation of phospho-signal transducer and activator of transcription 3 as well as a up-regulation of suppressor of cytokine signaling 3 upon leptin treatment, particularly in the arcuate nucleus. These data indicate alterations in the intracellular processing of the leptin signal under hypothyroid conditions and thereby unravel a novel mode of action by which TH affects energy metabolism.

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BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons

International Journal of Molecular Sciences ◽

10.3390/ijms21144947 ◽

2020 ◽

Vol 21 (14) ◽

pp. 4947

Author(s):

Tetsuya Yoshizumi ◽

Atsuhiko Kubo ◽

Hidetoshi Murata ◽

Masamichi Shinonaga ◽

Hiroshi Kanno

Keyword(s):

Stem Cells ◽

Amino Acid ◽

Cognitive Function ◽

Neuronal Differentiation ◽

Amino Acid Sequences ◽

Cytokine Signaling ◽

Epidermal Stem Cells ◽

Suppressor Of Cytokine Signaling ◽

Socs Proteins ◽

The Brain

The BC-box motif in suppressor of cytokine signaling 6 (SOCS6) promotes the neuronal differentiation of somatic stem cells, including epidermal stem cells. SOCS6 protein belongs to the group of SOCS proteins and inhibits cytokine signaling. Here we showed that epidermal stem cells were induced to differentiate into GABAnergic neurons by the intracellular delivery of a peptide composed of the amino-acid sequences encoded by the BC-box motif in SOCS6 protein. The BC-box motif (SLQYLCRFVI) in SOCS6 corresponded to the binding site of elongin BC. GABAnergic differentiation mediated by the BC-box motif in SOCS6 protein was caused by ubiquitination of JAK2 and inhibition of the JAK2-STAT3 pathway. Furthermore, GABAnergic neuron-like cells generated from epidermal stem cells were transplanted into the brain of a rodent ischemic model. Then, we demonstrated that these transplanted cells were GAD positive and that the cognitive function of the ischemic model rodents with the transplanted cells was improved. This study could contribute to not only elucidating the mechanism of GABAnergic neuronal differentiation but also to neuronal regenerative medicine utilizing GABAnergic neurons.

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