Characterization of a novel Fibroblast growth factor 10 (Fgf10) knock-in mouse line to target mesenchymal progenitors during embryonic development

Abstract

Fibroblast growth factor 10 (Fgf10) is a key regulator of diverse organogenetic programs during mouse development, particularly branching morphogenesis. Fgf10-null mice suffer from lung and limb agenesis as well as cecal and colonic atresia and are thus not viable. To date, the Mlcv1v-nLacZ-24 transgenic mouse strain (referred to as Fgf10 LacZ ), which carries a LacZ insertion 114 kb upstream of exon 1 of Fgf10 gene, has been the only strain to allow transient lineage tracing of Fgf10-positive cells. Here, we describe a novel Fgf10 Cre-ERT2 knock-in line (Fgf10 iCre ) in which a Cre-ERT2-IRES-YFP cassette has been introduced in frame with the ATG of exon 1 of Fgf10 gene. Our studies show that Cre-ERT2 insertion disrupts Fgf10 function. However, administration of tamoxifen to Fgf10 iCre ; Tomato flox double transgenic embryos or adult mice results in specific labeling of Fgf10-positive cells, which can be lineage-traced temporally and spatially. Moreover, we show that the Fgf10 iCre line can be used for conditional gene inactivation in an inducible fashion during early developmental stages. We also provide evidence that transcription factors located in the first intron of Fgf10 gene are critical for maintaining Fgf10 expression over time. Thus, the Fgf10 iCre line should serve as a powerful tool to explore the functions of Fgf10 in a controlled and stage-specific manner.

A human embryonic limb cell atlas resolved in space and time

“…5 h,j). This is consistent with expression in lineage tracing experiments in the mouse, where conditional knockdown leads to truncated, webbed digits 150 . FGF10 has been shown to induce chondrogenesis via FGFR2, which we found to be densely expressed in the chondrocyte progenitors (Fig.…”

Ex vivo analysis of the contribution of FGF10+ cells to airway smooth muscle cell formation during early lung development

“…Mice were kept in an SPF environment with free access to food and water ad libitum. Fgf10 CreERT2 knock‐in mice were generated, validated, and analyzed previously (El Agha et al, ; El Agha et al, ). Acta2‐CreERT2 transgenic mice (Wendling et al, ) were kindly provided by Dr. Pierre Chambon.…”

From snapshots to movies: Understanding early tooth development in four dimensions

“…Therefore, investigating dental mesenchymal dynamics would be a logical next step to further our understanding of tooth morphogenesis. Recently, tamoxifen-inducible Cre lines under control of promoters of early dental mesenchymal markers, such as Fgf10 and Msx1, have been generated, and these may be useful for future studies (El Agha et al, 2012;Lallemand et al, 2013). In parallel, the field has also begun to explore dental mesenchymal cell dynamics through combining ex vivo imaging with tissue recombination techniques (Mammoto et al, 2011;Li et al, 2016a).…”