Eric T. Hall's research while affiliated with St. Jude Children's Research Hospital and other places

Publications (14)

Article
Developmental tissue patterning and postdevelopmental tissue homeostasis depend upon controlled delivery of cellular signals called morphogens. Morphogens act in a concentration-and time-dependent manner to specify distinct transcriptional programs that instruct and reinforce cell fate. One mechanism by which appropriate morphogen signaling thresho...
Article
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During development and tissue homeostasis, cells must communicate with their neighbors to ensure coordinated responses to instructional cues. Cues such as morphogens and growth factors signal at both short and long ranges in temporal- and tissue-specific manners to guide cell fate determination, provide positional information, and to activate growt...
Article
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Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. The cytoneme morphogen transport model posits that specialized filopodia extend between morphogen-sending and responding cells to ensure that appropriate signaling thresholds are achieved. How morphogens are transported along and deployed from cyt...
Preprint
Full-text available
Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. Molecular mechanisms by which these signaling gradients are established and reinforced remain enigmatic. The cytoneme transport model posits that specialized filopodia extend between morphogen-sending and responding cells to ensure that appropriat...
Article
The Hedgehog (Hh) family of morphogens direct cell fate decisions during embryogenesis and signal to maintain tissue homeostasis after birth. Hh ligands harbor dual lipid modifications that anchor the proteins into producing cell membranes, effectively preventing ligand release. The transporter-like protein Dispatched (Disp) functions to release th...
Article
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Actomyosin contractility can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis. We identified that increased nonmuscle myosin II activation and cellular contraction inhibited Wnt target gene transcription in developing Drosophila imaginal disks. Genetic interactions st...
Article
Immunocytochemistry of cultured cells is a common and effective technique for determining compositions and localizations of proteins within cellular structures. However, traditional cultured cell fixation and staining protocols are not effective in preserving cultured cell cytonemes, long specialized filopodia that are dedicated to morphogen transp...
Preprint
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Mechanical forces can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis, but a molecular mechanism involving both in a developing epithelium and its homeostasis is lacking. We identified that increased non-muscle myosin II activation and cellular contraction inhibited...
Article
Full-text available
The Wnt/Wingless (Wg) pathway controls cell fate specification, tissue differentiation and organ development across organisms. Using an in vivo RNAi screen to identify novel kinase and phosphatase regulators of the Wg pathway, we identified subunits of the serine threonine phosphatase Protein phosphatase 4 (PP4). Knockdown of the catalytic and the...
Preprint
Full-text available
The Wnt/Wingless (Wg) pathway controls cell fate specification, tissue differentiation and organ development across organisms. Using an in vivo RNAi screen to identify novel kinase and phosphatase regulators of the Wg pathway, we identified subunits of the serine threonine phosphatase Protein phosphatase 4 (PP4). Knockdown of the catalytic and the...
Article
Wnt/Wingless (Wg) and Ras/MAPK signaling both play fundamental roles in growth, cell-fate determination, and when dysregulated, can lead to tumorigenesis. Several conflicting modes of interaction between Ras/MAPK and Wnt signaling have been identified in specific cellular contexts, causing synergistic or antagonistic effects on target genes. We fin...

Citations

... The area of the neural tube and the area of the progenitor domain were measured using the Segmented Line Tool in ImageJ. Expression domain areas were calculated by measuring the area of the indicated expression domain and normalizing it to the total area of the neural tube in each section analyzed (Hall et al., 2024). Three to five embryos were analyzed per genotype with five to eight sections analyzed per embryo. ...
... The expanding field of actin-based protrusions faces new limitations we need to overcome with the development of novel approaches. Some of the limitations are technical, such as the fact that cytonemes and TNTs are fragile structures damaged by classical fixation protocols, which has led to the publication of new optimized protocols (Abounit et al., 2015;Hall et al., 2022;Rogers and Scholpp, 2021). The low frequency of transfer via these structures also makes it difficult to reconcile live imaging and quantitative approaches. ...
... Therefore, trace Syt4 is insufficient for signaling. Second, Syt4 could be transferred by a non-EV pathway, such as conventional secretion, tunneling nanotubes, or cytonemes, and be distributed diffusely in the muscle such that we cannot detect its presence or degradation by cytoplasmic deGradFP (Dagar and Subramaniam, 2023;Daly et al., 2022). Third, it is possible that the muscle GAL4 drivers and UAS lines used in these previous rescue studies have some leaky expression in the neuron. ...
... Given that SHH, the only HH ligand expressed in the developing cerebellum, is produced by PCs, we explored a role for KIF17 in PC regulation of SHH localization and release. Initially, examination of Shh expression by RT-qPCR revealed that Shh transcripts are down-regulated in both We also examined levels of the HH coreceptor, BOC, which is expressed in PCs (5) and has been recently demonstrated to regulate SHH localization in cytonemes of NIH/3T3 cells (28). Notably, levels of Boc transcripts ( fig. ...
... Mechanistically, it was proposed that actomyosin activity at the cell-cell contacts mediates the effect of mechanical forces on Wnt/b-cat signaling (Hall et al., 2017;Hirata et al., 2017). Accordingly, myosin II inhibition with blebbistatin or abolishing the link between E-cadherin and the actin cytoskeleton, via a-cat knockdown, was shown to induce b-cat nuclear accumulation (Hirata et al., 2017). ...
... involvement of cytonemes in Hh signaling has been extended from insect to vertebrates by studies of the limb bud of chick embryo and cultured mouse embryonic fibroblasts (Sanders et al., 2013;Hall et al., 2020). The vertebrate homologs of the Drosophila Ihog proteins, Cdo and Boc, localize in cytonemes, and overexpression of either CDO or BOC increases the number of cytonemes detected on mammalian cells (Hall et al., 2020). ...
... Notably, the retained presence of the C-cholesterol moiety in serum-released Shh C is consistent with the proposed molecular mechanism by which Disp is thought to release Hh/Shh from the plasma membrane of producing cells. It is well known that all vertebrate and invertebrate Disp family members contain a sterol sensing domain (SSD) that is conserved in proteins that bind, transport, or respond to cellular sterols, such as SREBP cleavage activating protein (SCAP) and NPC1 [62][63][64]. The SSD extends into a hydrophobic surface channel that has been proposed to function as an open "slide" for lipophiles [65] for subsequent transfer to an acceptor [59]. ...
... Based on their results and earlier work that showed that plastin in lower eukaryotes stimulates actomyosin contractility, they postulated that PLS3 affects epidermal architecture by regulating keratinocyte mechanotransduction (Reichl et al., 2008;Ding et al., 2017;Dor-On et al., 2017). Even though osteoblast mineralization and skin development are very different processes, this does raise the question whether the decreased mineralization phenotype in PLS3 KD osteoblasts is secondary to decreased actomyosin-mediated contraction, which could lead to defective activation of downstream signaling pathways that directly or indirectly regulate mineralization (Clark et al., 2007;Zaidel-Bar et al., 2015;Hall et al., 2019;Khan et al., 2020). Alternatively, it was recently shown that osteoblast themselves can rearrange the collagen matrix, presumably to shape the osteocyte lacunae (Lu et al., 2018;Shiflett et al., 2019). ...
... Other characteristic features distinguishing TNTs-like structures from neurites or filopodia in culture are their sensitivity to commonly used fixation and ability to stretch above the substratum. (25,(51)(52)(53). We found that Rhes-induced TNTs in D2R-MSN are inset e-f, arrowhead). ...
... PPP4C is reported to regulate Wnt, BMP, and Hedgehog signaling pathways 8,22,31 . We specifically explored the relationship between PPP4C and Wnt signaling due to its fundamental function in AP patterning and neural crest formation. ...