PT  - JOURNAL ARTICLE
AU  - Yan Zhang
AU  - Henrik Ortsäter
AU  - Ines Martinez-Corral
AU  - Taija Mäkinen
TI  - <em>Cdh5</em>-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracing
AID  - 10.26508/lsa.202201561
DP  - 2022 Nov 01
TA  - Life Science Alliance
PG  - e202201561
VI  - 5
IP  - 11
4099  - https://www.life-science-alliance.org/content/5/11/e202201561.short
4100  - https://www.life-science-alliance.org/content/5/11/e202201561.full
SO  - Life Sci. Alliance2022 Nov 01; 5
AB  - The developmental origins of lymphatic endothelial cells (LECs) have been under intense research after a century-long debate. Although previously thought to be of solely venous endothelial origin, additional sources of LECs were recently identified in multiple tissues in mice. Here, we investigated the regional differences in the origin(s) of the dermal lymphatic vasculature by lineage tracing using the pan-endothelial Cdh5-CreERT2 line. Tamoxifen-induced labeling of blood ECs at E9.5, before initiation of lymphatic development, traced most of the dermal LECs but with lower efficiency in the lumbar compared with the cervical skin. By contrast, when used at E9.5 but not at E11.5, 4-hydroxytamoxifen, the active metabolite of tamoxifen that provides a tighter window of Cre activity, revealed low labeling frequency of LECs, and lymphvasculogenic clusters in the lumbar skin in particular. Temporally restricted lineage tracing thus reveals contribution of LECs of Cdh5-lineage–independent origin to dermal lymphatic vasculature. Our results further highlight Cre induction strategy as a critical parameter in defining the temporal window for stage-specific lineage tracing during early developmental stages of rapid tissue differentiation.