{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T21:03:12Z","timestamp":1780693392339,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,3]]},"group-title":"Developmental Biology","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["MRI 1228312"],"award-info":[{"award-number":["MRI 1228312"]}]},{"name":"National Science Foundation","award":["II NEW 1405767"],"award-info":[{"award-number":["II NEW 1405767"]}]},{"name":"National Science Foundation","award":["MRI 1725573"],"award-info":[{"award-number":["MRI 1725573"]}]},{"name":"National Science Foundation","award":["MRI 2018069"],"award-info":[{"award-number":["MRI 2018069"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Climate change is driving more frequent and severe heat events, yet the developmental mechanisms by which organisms anticipate and adapt to thermal stress remain poorly understood. In zebra finches (\n                  <jats:italic>Taeniopygia guttata<\/jats:italic>\n                  ), parents exposed to extreme heat emit distinctive \u201cheat call\u201d vocalizations during late incubation that trigger adaptive phenotypic responses in offspring, including altered growth, thermoregulation, and reproductive success. Recent transcriptomic analysis revealed that prenatal heat call exposure induces hypothalamic gene expression changes enriched in non-neuronal populations, but cellular heterogeneity has obscured which cell types are primary targets and the regulatory mechanisms underlying acoustic programming. Here, we performed single-nucleus multiome sequencing to generate a cell-type-resolved atlas of gene expression and chromatin accessibility in the late-stage embryonic zebra finch hypothalamus. We find that heat call exposure selectively remodels astrocyte regulatory landscapes, with most playback-responsive chromatin changes localized to glial populations like astrocytes, challenging neuron-centric models of developmental programming. Motif enrichment and gene regulatory network analysis showed Nuclear Factor I-C, AP-1, and Notch pathway components - canonical drivers of the gliogenic switch - coordinate this response. Chromatin co-accessibility analysis revealed extensive astrocyte-specific enhancer-promoter rewiring at developmental signaling hubs, and pseudotemporal analysis identified condition-associated shifts in developmental trajectories and astrocyte gene-expression dynamics consistent with altered gliogenic programs. In parallel, we identified sex-dimorphic regulation of transthyretin in glutamatergic neurons of the paraventricular nucleus, linking acoustic programming to thyroid-dependent neuroendocrine pathways. These findings suggest that prenatal acoustic experience engages astrocyte-selective epigenetic priming and neuroendocrine transcriptional responses that may reshape hypothalamic developmental programs under predicted thermal environments.\n                <\/jats:p>","DOI":"10.64898\/2026.06.01.729058","type":"posted-content","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:05:15Z","timestamp":1780513515000},"source":"Crossref","is-referenced-by-count":0,"title":["Multiome Profiling Reveals Astrocyte and Neuroendocrine Targets of Prenatal Acoustic Programming in Zebra Finch Embryos"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1160-7305","authenticated-orcid":false,"given":"Prakrit","family":"Subba","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA"},{"name":"Institute for Human Genetics, Clemson University, Greenwood, SC, 29646, USA"},{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Shankar","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Clemson University, Greenwood, SC, 29646, USA"},{"name":"Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Williams","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Clemson University, Greenwood, SC, 29646, USA"},{"name":"Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudy F. C.","family":"Mackay","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Clemson University, Greenwood, SC, 29646, USA"},{"name":"Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Freymuth","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Clemson University, Greenwood, SC, 29646, USA"},{"name":"Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie A.","family":"Shay","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Clemson University, Greenwood, SC, 29646, USA"},{"name":"Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Rees","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA"},{"name":"Department of Forestry and Environmental Conservation, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon R.","family":"Liedl","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Clayton","sequence":"additional","affiliation":[{"name":"Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA"},{"name":"Institute for Human Genetics, Clemson University, Greenwood, SC, 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026060513101177000_2026.06.01.729058v1.1","doi-asserted-by":"crossref","first-page":"9710","DOI":"10.1038\/s41467-025-65343-5","article-title":"Neuronal type-specific modulation of cognition and AP-1 signaling by early-life rearing conditions","volume":"16","year":"2025","journal-title":"Nat. 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