CREB Non-autonomously Controls Reproductive Aging through Hedgehog/Patched Signaling.

TitleCREB Non-autonomously Controls Reproductive Aging through Hedgehog/Patched Signaling.
Publication TypeJournal Article
Year of Publication2020
AuthorsTempleman, NM, Cota, V, Keyes, W, Kaletsky, R, Murphy, CT
JournalDev Cell
Volume54
Issue1
Pagination92-105.e5
Date Published2020 07 06
ISSN1878-1551
KeywordsAging, 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>

DOI10.1016/j.devcel.2020.05.023
Alternate JournalDev Cell
PubMed ID32544391
PubMed Central IDPMC7837322
Grant ListDP2 OD004402 / OD / NIH HHS / United States
P30 CA072720 / CA / NCI NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States