Title | CREB Non-autonomously Controls Reproductive Aging through Hedgehog/Patched Signaling. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Templeman, NM, Cota, V, Keyes, W, Kaletsky, R, Murphy, CT |
Journal | Dev Cell |
Volume | 54 |
Issue | 1 |
Pagination | 92-105.e5 |
Date Published | 2020 Jul 06 |
ISSN | 1878-1551 |
Keywords | Aging, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cyclic AMP Response Element-Binding Protein, Hedgehog Proteins, Oocytes, Patched Receptors, Reproduction, Signal Transduction, Transforming Growth Factor beta |
Abstract | <p>Evolutionarily conserved signaling pathways are crucial for adjusting growth, reproduction, and cell maintenance in response to altered environmental conditions or energy balance. However, we have an incomplete understanding of the signaling networks and mechanistic changes that coordinate physiological changes across tissues. We found that loss of the cAMP response element-binding protein (CREB) transcription factor significantly slows Caenorhabditis elegans' reproductive decline, an early hallmark of aging in many animals. Our results indicate that CREB acts downstream of the transforming growth factor β (TGF-β) Sma/Mab pathway in the hypodermis to control reproductive aging, and that it does so by regulating a Hedgehog-related signaling factor, WRT-10. Overexpression of hypodermal wrt-10 is sufficient to delay reproductive decline and oocyte quality deterioration, potentially acting via Patched-related receptors in the germline. This TGF-β-CREB-Hedgehog signaling axis allows a key metabolic tissue to communicate with the reproductive system to regulate oocyte quality and the rate of reproductive decline.</p> |
DOI | 10.1016/j.devcel.2020.05.023 |
Alternate Journal | Dev Cell |
PubMed ID | 32544391 |
PubMed Central ID | PMC7837322 |
Grant List | DP2 OD004402 / OD / NIH HHS / United States P30 CA072720 / CA / NCI NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States |