Tlx acts as a proangiogenic switch
by regulating extracellular assembly
of fibronectin matrices in retinal astrocytes
J. Clin. Invest. Akiyoshi Uemura, et al. 116:369 doi:10.1172/JCI25964 [
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Figure 6Tlx regulates formation of proangiogenic scaffolds by controlling extracellular deposition of fibronectin matrices in retinal astrocytes. (
A and
E) Whole-mount ISH for
VEGF (
A) or
fibronectin (
E) in P7 retinas of
Tlx–/– mice. The lower panels are magnifications of ISH (black) with immunostaining for PDGFRα (white). In contrast to the retained
VEGF expression over the astrocyte network,
fibronectin is expressed only in a small subset of astrocytes in
Tlx–/– retina. OD, optic disc. (
B) Whole-mount immunostaining for PECAM-1 in P16
Tlx–/– retinal cups 48 hours after intraocular injections of control Fc (upper panels) or VEGF Trap (lower panels). Right panels are the higher magnifications of hyaloid vessels shown in left panels. Persistent hyaloid vessels and their sprouts in
Tlx–/– eyes regress by neutralization of VEGF signals. (
C and
D) Immunostaining for PECAM-1 (green) and GFAP (red) in P14 retina of
Tlx–/– mouse. Ectopic vessels derived from hyaloids target retinal astrocytes (
C) but are not guided by the pre-existing astrocyte networks (
D). (
F and
G) Immunostaining for fibronectin (green) and PDGFRα (red) in
Tlx+/– (upper panels) and
Tlx–/– (lower panels) P7 retinas. In the astrocyte networks of
Tlx–/– retinas, fibronectin proteins are detected only in a punctate manner (
F). Note the retention of fibronectin proteins in perinuclear cytoplasmic regions of
Tlx–/– astrocytes (
G). Magnification, ×126 (upper panels of
A and
E), ×400 (lower panels of
A and
E), ×32 (
B, left panels), ×100 (
B, right panels), ×150 (
C), ×630 (
D), ×200 (
F), ×1260 (
G).
