Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function
- University of Colorado Anschutz Medical Campus, United States
- University of Oklahoma Health Sciences Center, United States
Abstract
Embryonic taste bud primordia are specified as taste placodes on the tongue surface and differentiate into the first taste receptor cells (TRCs) at birth. Throughout adult life, TRCs are continually regenerated from epithelial progenitors. Sonic hedgehog (SHH) signaling regulates TRC development and renewal, repressing taste fate embryonically, but promoting TRC differentiation in adults. Here, using mouse models, we show TRC renewal initiates at birth and coincides with onset of SHHs pro-taste function. Using transcriptional profiling to explore molecular regulators of renewal, we identified Foxa1 and Foxa2 as potential SHH target genes in lingual progenitors at birth, and show SHH overexpression in vivo alters FoxA1 and FoxA2 expression relevant to taste buds. We further bioinformatically identify genes relevant to cell adhesion and cell locomotion likely regulated by FOXA1;FOXA2, and show expression of these candidates is also altered by forced SHH expression. We present a new model where SHH promotes TRC differentiation by regulating changes in epithelial cell adhesion and migration.
Data availability
Sequencing data have been deposited in GEO under accession code GSE159941https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159941
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (R01DC012383)
- Linda A Barlow
National Institute on Deafness and Other Communication Disorders (Postdoc fellowship F32DC015958)
- Erin J Golden
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Valerie Horsley, Yale University, United States
Ethics
Animal experimentation: Male and female mice were maintained, bred, and embryos and pups at the University of Colorado Anschutz Medical Campus (CU AMC) in accordance with approved protocols #00150 and #52815(02)1C by the Institutional Animal Care and Use Committee at CU AMC. All animals were euthanized via chilling and CO2 prior to tissue harvest to minimize suffering.
Version history
- Received: October 14, 2020
- Accepted: May 18, 2021
- Accepted Manuscript published: May 19, 2021 (version 1)
- Version of Record published: June 2, 2021 (version 2)
Copyright
© 2021, Golden et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function
eLife 10:e64013.
https://doi.org/10.7554/eLife.64013
Further reading
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During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the murine fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.
