Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling

Huh, Sung Ho; Warchol, Mark E.; Ornitz, David M.

doi:10.7554/elife.05921

Cited by 71 publications

(103 citation statements)

References 52 publications

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“…Having discovered unclustered DC precursors prior to formation of mature DC, we next asked whether Fgf20 is required for induction of the pre-DC fate. To this end, we generated Fgf20 -ablated embryos by crossing viable and fertile Fgf20 Cre-GFP/Cre-GFP knockout mice with Fgf20 LacZ/+ mice (Huh et al, 2012, 2015). In E14.5 heterozygous Fgf20 Cre-GFP/+ control skins, we observed normal hair follicle development with multiple DC stages underneath GFP + Pc (Figures 6C and S6D).…”

Section: Resultsmentioning

confidence: 99%

“…Sox2 GFP (Ellis et al, 2004), Tbx18 H2BGFP (Grisanti et al, 2013) and Pdgfra H2BGFP (Hamilton et al, 2003) fluorescent reporter mice were generated as previously described. Fgf20 Cre-GFP and Fgf20 LacZ mice for Fgf20 knockout were generated as previously described (Huh et al, 2012; Huh et al, 2015). β-catenin epidermal-specific cKO were generated by mating β-catenin fl/fl (Brault et al, 2001) with K14-Cre (Dassule et al, 2000) mice.…”

Section: Star Methodsmentioning

confidence: 99%

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Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent

et al. 2019

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SUMMARY Cell fate transitions are essential for specification of stem cells and their niches, but the precise timing and sequence of molecular events during embryonic development are largely unknown. Here, we identify with 3D/4D microscopy unclustered precursors of dermal condensates (DC), signaling niches for epithelial progenitors in hair placodes. With population-based and single-cell transcriptomics, we define a molecular time-lapse from pre-DC fate specification through DC niche formation and establish the developmental trajectory as the DC lineage emerges from fibroblasts. Co-expression of downregulated fibroblast and upregulated DC genes in niche precursors reveals a transitory molecular state following a proliferation shutdown. Waves of transcription factor and signaling molecule expression then coincide with DC formation. Finally, ablation of epidermal Wnt signaling and placode-derived FGF20 demonstrates their requirement for pre-DC specification. These findings uncover a progenitor-dependent niche precursor fate and the transitory molecular events controlling niche formation and function.

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Section: Resultsmentioning

confidence: 99%

Section: Star Methodsmentioning

confidence: 99%

Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent

et al. 2019

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“…FGFR1 and FGFR2 have similar in vitro signaling potency and ligand response profiles to FGF9 and FGF18 (Zhang et al, 2006), ligands that have key roles in regulating skeletal development (Hung et al, 2016Liu et al, 2007Liu et al, , 2002Ohbayashi et al, 2002). In several tissues, including the limb bud, palate, lung, kidney, liver, cerebellum, epidermis and inner ear, Fgfr1 and Fgfr2 show significant functional redundancy (Böhm et al, 2010;Huh et al, 2015;Meyer et al, 2012;Ornitz and Itoh, 2015;Poladia et al, 2006;SimsLucas et al, 2011;Smith et al, 2012;White et al, 2006;Yang et al, 2010;Yu et al, 2015;Yu and Ornitz, 2008). To study the roles of FGFR signaling in the osteoprogenitor lineage, the Osx-GFP::Cre (Osx-Cre) allele was crossed to floxed alleles of Fgfr1 and Fgfr2 (Rodda and McMahon, 2006;Trokovic et al, 2003;Yu et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth

Karuppaiah

Lim

et al. 2016

Development

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Fibroblast growth factor (FGF) signaling is important for skeletal development; however, cell-specific functions, redundancy and feedback mechanisms regulating bone growth are poorly understood. FGF receptors 1 and 2 (Fgfr1 and Fgfr2) are both expressed in the osteoprogenitor lineage. Double conditional knockout mice, in which both receptors were inactivated using an osteoprogenitor-specific Cre driver, appeared normal at birth; however, these mice showed severe postnatal growth defects that include an ∼50% reduction in body weight and bone mass, and impaired longitudinal bone growth. Histological analysis showed reduced cortical and trabecular bone, suggesting cellautonomous functions of FGF signaling during postnatal bone formation. Surprisingly, the double conditional knockout mice also showed growth plate defects and an arrest in chondrocyte proliferation. We provide genetic evidence of a non-cell-autonomous feedback pathway regulating Fgf9, Fgf18 and Pthlh expression, which led to increased expression and signaling of Fgfr3 in growth plate chondrocytes and suppression of chondrocyte proliferation. These observations show that FGF signaling in the osteoprogenitor lineage is obligately coupled to chondrocyte proliferation and the regulation of longitudinal bone growth.

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“…Morphogens (and transcription factor genes) are depicted by a specific color and downstream genes that are predicted to be direct targets are connected by lines of the same color. If the putative association between a signaling pathway and a downstream affected gene is more likely to be indirect based on available evidence, then the two are connected by an interrupted line (shown as −−//−−) and dark blue dashed connector lines…”

Section: Secreted Signals Regulate Transcription Factors To Specify Dmentioning

confidence: 99%

The acquisition of positional information across the radial axis of the cochlea

Munnamalai

Fekete

2019

Developmental Dynamics

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The mammalian cochlea detects sound and transmits this information to the brain. A cross section through the cochlea reveals functionally distinct epithelial domains arrayed around the circumference of a fluid‐filled duct. Six major domains include two on the roof of the duct (Reissner's membrane medially and the stria vascularis laterally) and four across the floor of the duct, including the medial and lateral halves of the sensory domain, the organ of Corti. These radial domains are distinguishable in the embryonic cochlea by differential expression of transcription factors, and we focus here on a subset of the factors that can influence cochlear fates. We then move upstream of these genes to identify which of five signaling pathways (Notch, Fgf, Wnt, Bmp, and Shh) controls their spatial patterns of expression. We link the signaling pathways to their downstream genes, separating them by their radial position, to create putative gene regulatory networks (GRNs) from two time points, before and during the time when six radial compartments arise. These GRNs offer a framework for understanding the acquisition of positional information across the radial axis of the cochlea, and to guide therapeutic approaches to repair or regenerate distinct cochlear components that may contribute to hearing loss.

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Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling

Cited by 71 publications

References 52 publications

Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent

Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent

FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth

The acquisition of positional information across the radial axis of the cochlea

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