Abstract
The olfactory epithelium (OE) is composed of olfactory sensory neurons (OSNs), sustentacular supporting cells, and several types of non-neuronal cells. Stem and progenitor cells are located basally, and are the source of all cell types needed to maintain OE homeostasis. Here, we report that Ascl3, a basic helix-loop-helix transcription factor, is expressed in the developing OE. Lineage tracing experiments demonstrate that the non-neuronal microvillar cells and Bowman’s glands are exclusively derived from Ascl3+ progenitor cells in the OE during development. Following chemically-induced injury, Ascl3 expression is activated in a subset of horizontal basal cells (HBCs), which repopulate all microvillar cells and Bowman’s glands during OE regeneration. After ablation of Ascl3-expressing cells, the OE can regenerate, but lacks the non-neuronal microvillar and Bowman’s gland support cells. These results demonstrate that Ascl3 marks progenitors that are lineage-committed strictly to microvillar cells and Bowman’s glands, and highlight the requirement for these cell types to support OE homeostasis.
Highlights
Ascl genes, members of the achaete scute-like complex family, are basic helix-loop-helix transcription factors, which are expressed in progenitor cells of various tissues at the time of cell type specification
EGFPpositive cells were detectable throughout embryonic development, at E14.5, E16.5 and E18.5, in cells localized at the apical region of the developing olfactory epithelium (OE) (Fig. 1B)
We identify a distinct cell lineage marked by transient expression of Ascl[3] that is committed exclusively to microvillar cells and Bowman’s glands of the OE
Summary
Members of the achaete scute-like complex family, are basic helix-loop-helix transcription factors (bHLH), which are expressed in progenitor cells of various tissues at the time of cell type specification. Characterized member of the family, is a marker of progenitor cells in the salivary glands, and Ascl3-expressing precursor cells generate both duct and acinar cells in vitro[27,28,29]. We demonstrate that Ascl[3] is expressed in the OE, and marks precursors of the non-neuronal microvillar cells and Bowman’s glands during development and regeneration. We report that Ascl[3] expression is activated in progenitors during development, and in a subset of HBCs immediately after injury, which generate all microvillar cells and the Bowman’s glands. Our data provide new insight into the lineage of non-neuronal support cells, and their requirement for OE homeostasis
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