title: Enpp2/Autotaxin in dermal papilla precursors is dispensable for hair follicle morphogenesis.
abstract: Systematic ablation of previously identified dermal papilla (DP) signature genes in embryonic DP precursors will reveal their functional roles during hair follicle morphogenesis. In this study, we validate Enpp2/Autotaxin as one of the highest expressed signature genes in postnatal DP, and demonstrate specific expression of this lysophosphatidic acid (LPA)-generating enzyme in embryonic dermal condensates. We further identify dermal and epidermal expression of several LPA receptors, suggesting that LPA signaling could contribute to follicle morphogenesis in both mesenchymal and epithelial compartments. We then use the recently characterized Cre-expressing Tbx18 knock-in line to conditionally ablate Enpp2 in embryonic DP precursors. Despite efficient gene knockout in embryonic day 14.5 (E14.5) dermal condensates, morphogenesis proceeds regularly with normal numbers, lengths, and sizes of all hair follicle types, suggesting that Enpp2 is not required for hair follicle formation. To interrogate DP signature gene expression, we finally isolate control and Enpp2-null DP precursors and identify the expression and upregulation of LIPH, an alternative LPA-producing enzyme, suggesting that this gene could functionally compensate for the absence of Enpp2. We conclude that future coablation of both LPA-producing enzymes or of several LPA receptors may reveal the functional role of LPA signaling during hair follicle morphogenesis.
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Grisanti
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Amelie
authors.initials: A
authors.lastname: Rezza
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Clavel
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sennett
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: michael.rendl@mssm.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Rendl
mesh_terms: D000818:Animals; D020405:Dermis / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018859:Hair Follicle / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology; D000099189:Lysophospholipase D
chemical_list: D008049:Lipase; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D049368:Receptors, Lysophosphatidic Acid; D020825:T-Box Domain Proteins; D000099189:Lysophospholipase D; C420983:Tbx18 protein, mouse; C584508:lipase H, mouse; C032881:lysophosphatidic acid