Expression patterns of ShcD and Shc family adaptor proteins during mouse embryonic development

Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
Developmental Dynamics (Impact Factor: 2.38). 01/2011; 240(1):221-31. DOI: 10.1002/dvdy.22506
Source: PubMed


The Src homology and collagen (Shc) proteins function as molecular adaptors in signaling pathways mediated by a variety of cell surface receptors. Of the four mammalian Shc proteins, ShcD is the least characterized. To this end, ShcD expression was documented and compared to that of other Shc family proteins. In the developing mouse embryo, expression of ShcD overlaps with that of other Shc proteins in the central nervous system, with specific distribution in post-mitotic neurons. In addition, robust ShcD expression is seen within differentiated epithelial cells of several organs, as well as in skeletal and cardiac muscle, and various tissues of neural crest origin. Interestingly, all Shc family members are expressed in hypertrophic chondrocytes, the first report of Shc protein expression in the developing skeleton. The unique tissue distribution patterns of Shc proteins likely contribute to their complex tissue-specific signaling functions during embryogenesis.

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Available from: Melanie Wills, Nov 24, 2015
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    • "ESCs are an invaluable tool to dissect the role of signaling molecules involved in development, as many studies have shown that when they differentiate, the events that occur in vitro faithfully recapitulate those in vivo [21–24]. In order to gain insight into the physiological function of ShcD and based on its high expression in the adult and developing brain [9, 25], we differentiated ESCs to neural lineages and found that ShcD is transiently upregulated during the early time-window of differentiation corresponding to the ESC to epiblast stem cells (EpiSCs) transition and is re-expressed when cells have acquired neural identity. "
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    ABSTRACT: The Shc family of adaptor proteins are crucial mediators of a plethora of receptors such as the tyrosine kinase receptors, cytokine receptors, and integrins that drive signaling pathways governing proliferation, differentiation, and migration. Here, we report the role of the newly identified family member, ShcD/RaLP, whose expression in vitro and in vivo suggests a function in embryonic stem cell (ESC) to epiblast stem cells (EpiSCs) transition. The transition from the naïve (ESC) to the primed (EpiSC) pluripotent state is the initial important step for ESCs to commit to differentiation and the mechanisms underlying this process are still largely unknown. Using a novel approach to simultaneously assess pluripotency, apoptosis, and proliferation by multiparameter flow cytometry, we show that ESC to EpiSC transition is a process involving a tight coordination between the modulation of the Oct4 expression, cell cycle progression, and cell death. We also describe, by high-content immunofluorescence analysis and time-lapse microscopy, the emergence of cells expressing caudal-related homeobox 2 (Cdx2) transcription factor during ESC to EpiSC transition. The use of the ShcD knockout ESCs allowed the unmasking of this process as they presented deregulated Oct4 modulation and an enrichment in Oct4-negative Cdx2-positive cells with increased MAPK/extracellular-regulated kinases 1/2 activation, within the differentiating population. Collectively, our data reveal ShcD as an important modulator in the switch of key pathway(s) involved in determining EpiSC identity. STEM CELLS2012;30:2423-2436.
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    • "SHC4 therefore appears to be directly repressed by MITF suggesting that MITF both activates and represses transcription in a promoter context-dependent manner similar to POU3F2 discussed above. SHC4 (also known as SHCD (Hawley et al., 2011), or RaLP, retinoic acid-like inducible like protein) belongs to the family of SRC homology and collagen (Shc) signal transduction adaptor proteins. These proteins share a common organisation with an N-terminal phosphotyrosine-binding (PTB) domain, a central region rich in proline and glycine residues (CH1) and a C-terminal SRC homologue 2 (SH2) domain (Pasini et al., 2009). "

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