TABLE 4.

Molecular actors in capillary remodeling in vivo.

Capillary pruning
Mechanosensors
Piezo 1 YAP/TAZ K+ channel Kir2.1	LOF, probable decreased vessel regression in mouse retina Nuclear location required for vessel regression in zebrafish LOF, reduced EC alignment and vessel regression in mouse retina	Ranade et al. (2014) Nagasawa-Masuda and Terai (2017) Boriushkin et al. (2019)
Notch, Wnt, BMP
Notch Non-canon Wnt Alk1 Endoglin Smad1/5	LOF, EC elongation and decreased capillary regression in mouse retina LOF, increased sensitivity to SS-induced regression in vivo LOF, hyper-vascularization and AV malformations in mouse retina LOF, EC shape changes (no alignment), directed migration and AV shunts LOF, reduced vessel regression and loop formation in mouse retina	Lobov et al. (2011), Mack et al. (2017) Franco et al. (2016) Larrivee et al. (2012) Jin et al. (2017); Sugden et al. (2017) Benn et al. (2020)
IFT88	LOF, premature and random vessel regression in mouse retina	Vion et al. (2018)
Signal transducers
CDS2 Rac1	LOF, increased vessel regression in zebrafish and postnatal mouse retina LOF, EC migration in vivo and defective vessel pruning in zebrafish brain	Zhao et al. (2019) Chen et al. (2012)
Soluble factors
VEGF	Predicted contribution to capillary pruning in mouse retina	Watson et al. (2012)
Capillary splitting
ECM-related
MT1-MMP TSP1	LOF, decreased vessel splitting during mouse colitis in vivo LOF, decreased vessel splitting in mouse colitis	Esteban et al. (2020) Esteban et al. (2020)
Soluble factors
VEGF Nitric oxide/eNOS	Promotes vessel splitting in skeletal muscle and CAM LOF, reduces capillary splitting in the skeletal muscle and correlates with less capillary splitting in mouse colitis	Baum et al. (2010); Gianni-Barrera et al. (2013) Esteban et al. (2020), Williams et al. (2006a)
Other vascular remodeling events
Signal transducers
Dach1 ApelinR Erk5 Nck p130Cas	GOF/LOF, EC polarization, alignment and migration against flow and LOF, impaired embryonic arterial patterning Required for EC polarization in vitro and in vivo in zebrafish LOF, Disorganized and rounded ECs in vivo LOF, impaired EC front-rear polarity and VEGF-directed migration in vivo; no impact in vessel regression in retina LOF, less focal adhesion turnover and EC directed migration in vitro	Chang et al. (2017) Kwon et al. (2016) Nithianandarajah-Jones et al. (2014), Spiering et al. (2009) Chaki and Rivera (2013), Dubrac et al. (2016) Spiering et al. (2009), Zaidel-Bar et al. (2005)
ECM-related
Nrp1	Enables EC filopodia via cdc42 in zebrafish and mouse retina and regulates EC shape, cell contacts, and actin in collective migration in zebrafish	Fantin et al. (2015), Hamm et al. (2016)

Representative molecular players with reported or suggested actions in capillary regression, splitting or other vascular remodeling events in vivo. EC, endothelial cells; GOF, gain-of-function; LOF, loss-of-function.