Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of Wnt signaling.

The cerebral cortex performs complex cognitive functions at the expense of tremendous energy consumption. Blood vessels in the brain are known to form stereotypic patterns that facilitate efficient oxygen and nutrient delivery. Yet little is known about how vessel development in the brain is normally regulated. Radial glial neural progenitors are well known for their central role in orchestrating brain neurogenesis. Here we show that, in the late embryonic cortex, radial glial neural progenitors also play a key role in brain angiogenesis, by interacting with nascent blood vessels and regulating vessel stabilization via modulation of canonical Wnt signaling. We find that ablation of radial glia results in vessel regression, concomitant with ectopic activation of Wnt signaling in endothelial cells. Direct activation of Wnt signaling also results in similar vessel regression, while attenuation of Wnt signaling substantially suppresses regression. Radial glial ablation and ectopic Wnt pathway activation leads to elevated endothelial expression of matrix metalloproteinases, while inhibition of metalloproteinase activity significantly suppresses vessel regression. These results thus reveal a previously unrecognized role of radial glial progenitors in stabilizing nascent brain vascular network and provide novel insights into the molecular cascades through which target neural tissues regulate vessel stabilization and patterning during development and throughout life.

Anatomical survey of terminal branching patterns of superficial branch of radial nerve in fetuses.

BACKGROUND: Regional anesthesia plays a key role in elective as well as emergency orthopedic and other surgeries in children. However, peripheral nerve blocks are quite challenging in children due to lack of precise anatomical knowledge of the course and distribution of these nerves. The purpose of this study was to explore the terminal branches of the superficial branch of the radial nerve in fetuses. The relationship of the superficial branch of the radial nerve with cephalic vein and surrounding tendons was also observed. METHODS: A total of 60 upper extremities (42 males and 18 females) of 30 spontaneously aborted fetuses (32-40 weeks) were dissected to expose the superficial branch of the radial nerve in the distal forearm and hand. RESULTS: Three patterns of distribution based on the total area of the dorsum of the hand innervated were observed. Type 1 (66.7%): superficial branch of radial nerve (SBRN) innervated lateral two-and-a-half digits; Type 2 (23.3%): SBRN innervated lateral three digits; Type 3 (10%): SBRN innervated lateral three-and-a-half digits. The cephalic vein was seen to intersect the nerve more than twice along its course. CONCLUSIONS: Detailed knowledge of the distribution patterns of terminal branches of superficial branch of radial nerve in hand will enhance the success rate of regional blocks or hand surgeries and minimize the postoperative complications due to injury to nerve or vascular structures.

The digital venous drainage in the human embryonic hand.

The histogenesis and morphology of the digital venous drainage in human embryonic and fetal hands, aged from 6 to 12 weeks, were studied by light microscopy in 18 fingers. In the sixth week, capillaries could be identified around the cartilaginous models of the phalanges. By the ninth week, the neurovascular bundles were identifiable in the palmar part of the finger. In 12 week fetuses, all of the superficial and deep vascular venous system could be seen easily in the palmar aspect of the finger in positions similar to those in the adult hand. However, the arch systems, present on the dorsum of the finger in the adult hand, were not yet differentiated.

Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells.

Although the local environment is known to regulate neural stem cell (NSC) maintenance in the central nervous system, little is known about the molecular identity of the signals involved. Chondroitin sulfate proteoglycans (CSPGs) are enriched in the growth environment of NSCs both during development and in the adult NSC niche. In order to gather insight into potential biological roles of CSPGs for NSCs, the enzyme chondroitinase ABC (ChABC) was used to selectively degrade the CSPG glycosaminoglycans. When NSCs from mouse E13 telencephalon were cultivated as neurospheres, treatment with ChABC resulted in diminished cell proliferation and impaired neuronal differentiation, with a converse increase in astrocytes. The intrauterine injection of ChABC into the telencephalic ventricle at midneurogenesis caused a reduction in cell proliferation in the ventricular zone and a diminution of self-renewing radial glia, as revealed by the neurosphere-formation assay, and a reduction in neurogenesis. These observations suggest that CSPGs regulate neural stem/progenitor cell proliferation and intervene in fate decisions between the neuronal and glial lineage.

Engrailed is expressed in larval development and in the radial nervous system of Patiriella sea stars.

We documented expression of the pan-metazoan neurogenic gene engrailed in larval and juvenile Patiriella sea stars to determine if this gene patterns bilateral and radial echinoderm nervous systems. Engrailed homologues, containing conserved En protein domains, were cloned from the radial nerve cord. During development, engrailed was expressed in ectodermal (nervous system) and mesodermal (coeloms) derivatives. In larvae, engrailed was expressed in cells lining the larval and future adult coeloms. Engrailed was not expressed in the larval nervous system. As adult-specific developmental programs were switched on during metamorphosis, engrailed was expressed in the central nervous system and peripheral nervous system (PNS), paralleling the pattern of neuropeptide immunolocalisation. Engrailed was first seen in the developing nerve ring and appeared to be up-regulated as the nervous system developed. Expression of engrailed in the nerve plexus of the tube feet, the lobes of the hydrocoel along the adult arm axis, is similar to the reiterated pattern of expression seen in other animals. Engrailed expression in developing nervous tissue reflects its conserved role in neurogenesis, but its broad expression in the adult nervous system of Patiriella differs from the localised expression seen in other bilaterians. The role of engrailed in patterning repeated PNS structures indicates that it may be important in patterning the fivefold organisation of the ambulacrae, a defining feature of the Echinodermata.

[Formation of the neurovascular connections in human forearm muscles]. / Stanovlenie sosudisto-nervnykh sviazei v myshtsakh predplech'ia cheloveka.

The data on the vascular bed formation and construction of intraorganic nerves of the human forearm muscles in embryogenesis are presented. It is stated that in the process of development the following stages can be revealed in microvessels of the neural fasciculi: a) prevascular (up to 3 months of the intrauterine development, b) initial stage of formation of neuromuscular connections (3--5 months of embryogenesis), c) developed stage (the second half of embryogenesis). In the intraorganic nerves, microvessels are arranged in several layers. The first is situated on the surface of the neural fasciculi, outside the perineurium; the second is situated in the bulk of the latter, between its cellular-fibrillar layers. The third group of the microvessels is within the nerve, between its fibres. In thin fasciculi they are presented by single microvessels. In thick and middle-sized intraorganic nerves, there are several similar vascular capillaries, connecting with each other, they form capillary loops.