Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigmentation biology. We show that IFN-γ signaling impedes maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. Withdrawal of IFN-γ signal spontaneously restores normal cellular programming. This effect in melanocytes is mediated by IFN regulatory factor-1 and is not dependent on the central regulator microphthalmia-associated transcription factor. Chronic IFN-γ signaling shows a clear hypopigmentation phenotype in both mouse and human skin. Interestingly, IFN-γ KO mice display a delayed recovery response to restore basal state of epidermal pigmentation after UVinduced tanning. Together, our studies delineate a new spatiotemporal role of the IFN-γ signaling network in skin pigmentation homeostasis, which could have implications in various cutaneous depigmentary and malignant disorders.interferon | melanin | gene regulation | detanning

One of the striking aspects of stem cells is their ability to self-renew to maintain the adequate pool over extended periods and differentiate into distinct cell types on demand to sustain the tissue growth and repair by supplying new cells. Arabidopsis plant harbors pluripotent stem cells in the central zone (CZ) of the shoot apex. The daughters of these cells upon cell division move towards the peripheral zone (PZ). At the flanks of the meristem, they form lateral organs. Cells that get displaced underneath CZ become part of the rib-meristem (RM).RM gives rise to stem tissue and vascular cell types in higher plants. Despite the three decades of genetic research work, our understanding of how stem cells differentiate into PZ and RM cell types is inadequate. Here, we show that locally produced auxin in combination with transportis essential for stem cell differentiation and organogenesis in the shoot apex.WUSCHEL, a homeodomain transcription factor, negatively regulates auxin biosynthesis in the stem cell niche to maintain the long-term pluripotency of shoot stem cells. Our findings reveal the role of local auxin biosynthesis in stem cell differentiation and how WUSCHEL regulates auxin signaling to promote stem cell fate in the shoot apex. Main textIn shoot apical meristem (SAM), stem cell proliferation and exit are strictly controlled by cell-cell signaling network controlled by receptor like kinase CLAVATA1 (CLV1) and its ligand CLAVATA3 (CLV3) 1,2 . CLV3 binds to CLV1 and initiates the signaling cascade, which restricts the expression of WUSCHEL (WUS) in the organizing center 3-6 .WUS protein moves from its site of synthesis through plasmodesmata and directly activates CLV3 in CZ and also represses genes involved in differentiation 7-9 .Thus, WUS not only specifies stem cells in apical meristem but also serves the central hub around that patterns of gene expression are established to specify CZ, PZ, and RM to form a functional SAM.Here, we extend our previous observation of live-imaging to show that the culmination of auxin signaling in PZ is contributed by local auxin biosynthesis besides polar transport, and together they control stem cell differentiation in SAM. To maintain the fate of stem cells, WUS negatively regulates auxin responses in the CZ by directly regulating auxin biosynthesis and signaling genes to counter the differentiation pathways. Furthermore, we show that the enlarged CZ in clv3 mutant plants maintains DII-Venus stably, suggesting that the stem cell fate and auxin signaling are dynamically regulated to maintain the overall SAM organization. Results TAA1 and TAR2 are expressed in shootA previous live-imaging study has shown that transient downregulation of WUS in the stem cell niche results in higher auxin responses in the PZ with ectopic stem cell differentiation,

One of the challenges in developmental biology is to understand how the expression pattern of TFs linked to cell fate specification and tissue specialization are established and maintained. In angiosperms, cell fate specification events first take place in embryonic development. Lateral organs are formed in the shoot apex in postembryonic development. Cell type specifications occur independently in the newly formed organs with barring a few exceptions (Barton, 2010).

Background: Neural crest cells (NCCs) by responding to several signals and paracrine factors get differentiated into different lineages like peripheral nervous system (PNS), chondrocytes, myofibroblast, endocrine, melanocytes, etc., Melanocytes are pigment-producing cells that share a common origin, paracrine factors (Wnt, FGF, and BMP), and transcription factors (TFs) with the neurons of the nervous system. Objective: Neuronal model for neurodegenerative disorders are limited because of their nonhuman origin and transformation. In this review we propose the use melanocyte as a model system to study neurodegenerative studies. Method: Systematic Literature Review. Results: The similarity between neural crest-derived melanocytes and neurons, makes melanocyte an important model to study several neurodegenerative disorders like Alzheimer’s disease and Parkinson’s disorder. Conclusion: Melanocytes and neurons share common origin i.e. both arise from NCC and share identical signalling molecules and pathways. Neural crest-derived melanocytes can thus serve as a promising model system to study normal and pathological behaviour of less accessible neurons.

Skin pigmentation occurs through an intricate network of pathways involving several signaling and regulatory molecules. The homeostatic mechanisms controlling melanogenesis is of great importance since prolonged activation of melanin synthesis could have disastrous consequences to the skin. We used the small molecules forskolin and IBMX, two activators of cAMP levels, to induce melanogenesis in B16 melanoma cells. Treatment with forskolin and IBMX led to increased tyrosinase protein levels and enzyme activity, hyper‐dendricity, transcriptional upregulation of melanin biosynthetic pathway genes and melanin accumulation. Electron microscopic imaging showed that the two small molecules enhanced the maturation of melanosomes. To identify genome‐wide transcriptomic changes, we carried out a time‐course microarray analysis of B16 melanoma cells treated with forskolin and IBMX. Microarray data analysis showed that a large number of genes are commonly regulated by forskolin and IBMX. Hierarchical clustering analysis showed a temporal pattern of expression of ~1620 genes. DAVID pathway analysis yielded several genes involved in melanosome biogenesis, cell cycle, inflammation and small solute transporters enriched during melanogenesis. Moreover, the hyper‐pigmenting cells contained elevated ROS level consistent with the melanogenesis itself being a pro‐oxidative process indicating a connection between melanogenesis and oxidative stress in melanocytes. A large number of differentially expressed genes belonged to the SLC small molecule transporter family genes. siRNA‐mediated silencing of two of the novel transporter genes led to impaired pigmentation indicating a key role of the SLC genes. Moreover, we identified several differentially expressed genes encoding chromatin modulators and transcription factor genes including MITF, a master regulator of melanocyte lineage. Microarray profiling of B16 cells upon silencing with siMITF identified a large number of MITF‐independent genes. Together our study provided an integrated view of the transcriptome involved in melanogenesis that could facilitate the understanding of the pathogenesis of pigmentation disorders.Support or Funding InformationGenotypic Technology for microarray hybridization CSIR‐NMITLI, DST‐PURSE and DBT for fundingThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.