The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle
Recent studies indicate that many developing tissues modify glycolysis to favor lactate synthesis (Agathocleous et al., 2012; Bulusu et al., 2017; Gu et al., 2016; Oginuma et al., 2017; Sá et al., 2017; Wang et al., 2014; Zheng et al., 2016), but how this promotes development is unclear. Using forwa...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/56301 |
| _version_ | 1811227608571969536 |
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| author | Husniye Kantarci Yunzi Gou Bruce B Riley |
| author_facet | Husniye Kantarci Yunzi Gou Bruce B Riley |
| author_sort | Husniye Kantarci |
| collection | DOAJ |
| description | Recent studies indicate that many developing tissues modify glycolysis to favor lactate synthesis (Agathocleous et al., 2012; Bulusu et al., 2017; Gu et al., 2016; Oginuma et al., 2017; Sá et al., 2017; Wang et al., 2014; Zheng et al., 2016), but how this promotes development is unclear. Using forward and reverse genetics in zebrafish, we show that disrupting the glycolytic gene phosphoglycerate kinase-1 (pgk1) impairs Fgf-dependent development of hair cells and neurons in the otic vesicle and other neurons in the CNS/PNS. Fgf-MAPK signaling underperforms in pgk1- / - mutants even when Fgf is transiently overexpressed. Wild-type embryos treated with drugs that block synthesis or secretion of lactate mimic the pgk1- / - phenotype, whereas pgk1- / - mutants are rescued by treatment with exogenous lactate. Lactate treatment of wild-type embryos elevates expression of Etv5b/Erm even when Fgf signaling is blocked. However, lactate’s ability to stimulate neurogenesis is reversed by blocking MAPK. Thus, lactate raises basal levels of MAPK and Etv5b (a critical effector of the Fgf pathway), rendering cells more responsive to dynamic changes in Fgf signaling required by many developing tissues. |
| first_indexed | 2024-04-12T09:44:57Z |
| format | Article |
| id | doaj.art-f7013f77894643c294e04862ed7be0db |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:44:57Z |
| publishDate | 2020-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f7013f77894643c294e04862ed7be0db2022-12-22T03:37:59ZengeLife Sciences Publications LtdeLife2050-084X2020-04-01910.7554/eLife.56301The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicleHusniye Kantarci0Yunzi Gou1https://orcid.org/0000-0002-3105-252XBruce B Riley2https://orcid.org/0000-0001-6471-7965Biology Department, Texas A&M University, College Station, United StatesBiology Department, Texas A&M University, College Station, United StatesBiology Department, Texas A&M University, College Station, United StatesRecent studies indicate that many developing tissues modify glycolysis to favor lactate synthesis (Agathocleous et al., 2012; Bulusu et al., 2017; Gu et al., 2016; Oginuma et al., 2017; Sá et al., 2017; Wang et al., 2014; Zheng et al., 2016), but how this promotes development is unclear. Using forward and reverse genetics in zebrafish, we show that disrupting the glycolytic gene phosphoglycerate kinase-1 (pgk1) impairs Fgf-dependent development of hair cells and neurons in the otic vesicle and other neurons in the CNS/PNS. Fgf-MAPK signaling underperforms in pgk1- / - mutants even when Fgf is transiently overexpressed. Wild-type embryos treated with drugs that block synthesis or secretion of lactate mimic the pgk1- / - phenotype, whereas pgk1- / - mutants are rescued by treatment with exogenous lactate. Lactate treatment of wild-type embryos elevates expression of Etv5b/Erm even when Fgf signaling is blocked. However, lactate’s ability to stimulate neurogenesis is reversed by blocking MAPK. Thus, lactate raises basal levels of MAPK and Etv5b (a critical effector of the Fgf pathway), rendering cells more responsive to dynamic changes in Fgf signaling required by many developing tissues.https://elifesciences.org/articles/56301statoacoustic ganglionsensory epitheliumENU mutagenesisCRISPR/Cas9etv5bMAPK/Erk |
| spellingShingle | Husniye Kantarci Yunzi Gou Bruce B Riley The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle eLife statoacoustic ganglion sensory epithelium ENU mutagenesis CRISPR/Cas9 etv5b MAPK/Erk |
| title | The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle |
| title_full | The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle |
| title_fullStr | The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle |
| title_full_unstemmed | The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle |
| title_short | The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle |
| title_sort | warburg effect and lactate signaling augment fgf mapk to promote sensory neural development in the otic vesicle |
| topic | statoacoustic ganglion sensory epithelium ENU mutagenesis CRISPR/Cas9 etv5b MAPK/Erk |
| url | https://elifesciences.org/articles/56301 |
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