MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons.

Bone morphogenetic protein (BMP) signaling has emerged as an important regulator of sensory neuron development. Using a three-generation forward genetic screen in mice we have identified Megf8 as a novel modifier of BMP4 signaling in trigeminal ganglion (TG) neurons. Loss of Megf8 disrupts axon guidance in the peripheral nervous system and leads to defects in development of the limb, heart, and left-right patterning, defects that resemble those observed in Bmp4 loss-of-function mice. Bmp4 is expressed in a pattern that defines the permissive field for the peripheral projections of TG axons and mice lacking BMP signaling in sensory neurons exhibit TG axon defects that resemble those observed in Megf8 (-/-) embryos. Furthermore, TG axon growth is robustly inhibited by BMP4 and this inhibition is dependent on Megf8. Thus, our data suggest that Megf8 is involved in mediating BMP4 signaling and guidance of developing TG axons. DOI:http://dx.doi.org/10.7554/eLife.01160.001.

High EphA3 expressing ophthalmic trigeminal sensory axons are sensitive to ephrin-A5-Fc: implications for lobe specific axon guidance.

The ophthalmic, maxillary and mandibular axon branches of the trigeminal ganglion provide cutaneous sensory innervation to the vertebrate face. In the chick embryo, the trigeminal ganglion is bilobed, with ophthalmic axons projecting from the ophthalmic lobe, while maxillary and mandibular projections emerge from the maxillomandibular lobe. To date, target tissue specific guidance cues that discriminately guide the axon projections from the two trigeminal ganglion lobes are unknown. EphA receptor tyrosine kinases and ephrin-A ligands are excellent candidates for this process as they are known to mediate axon guidance in the developing nervous system. Accordingly, the expression of EphAs and ephrin-As was investigated at stages 13, 15, 20 of chick embryogenesis when peripheral axons from the trigeminal ganglion are pathfinding. EphA3 is expressed highly in the ophthalmic trigeminal ganglion lobe neurons in comparison to maxillomandibular trigeminal ganglion lobe neurons. Furthermore, from stages 13-20 ephrin-A2 and ephrin-A5 ligands are only localized to the mesenchyme of the first branchial arch (maxillary and mandibular processes), the target fields for maxillomandibular trigeminal ganglion axons. We found that ophthalmic and not maxillomandibular lobe axons were responsive to ephrin-A5-Fc utilizing a substratum choice assay. The implication of these results is that EphA3 forward signaling in ophthalmic sensory axons may be an important mechanism in vivo for lobe specific guidance of trigeminal ganglion ophthalmic projections.

Anuran postnasal wall homology: an experimental extirpation study.

The nasal placode was extirpated unilaterally in Gosner stage 18-20 embryos of Rana sylvatica, R. palustris and R. pipiens, in order to test alternative proposed schemes of homology for the ethmoidal attachment of the palatoquadrate in anurans and urodeles. Absence of the nasal sac has no pronounced effect on the formation of larval chondrocranial structures. In contrast, in metamorphosed animals the lamina orbitonasalis and inferior prenasal process are the only nasal capsule structures present on the operated side. The medial nasal branch of the deep ophthalmic nerve passes forward over the dorsal surface of the lamina orbitonasalis, rather than through an orbitonasal foramen. Comparison with previous experimental work on urodeles supports the traditional homology of the anuran lamina orbitonasalis with the antorbital process of urodeles and other vertebrates.

The composition of trigeminal nerve branches in normal adult chickens and after debeaking at different ages.

The long term effects of amputation of the tip of the beak were studied in adult hens that were debeaked on the day of hatching, at the age of 8 d and at 6 wk, by EM analysis of fibre spectra of the medial branch of the ophthalmic nerve and of the intramandibular nerve. Three categories of fibre were distinguished for further analysis, i.e. unmyelinated axons, small myelinated fibres and large myelinated fibres. In normal birds the ophthalmic nerve contains relatively more large fibres than the intramandibular nerve. Amputation consistently results in a reduction of the number of large fibres and a substantial increase in the number of small myelinated fibres. The proportion of unmyelinated axons is rather variable, but is not affected by beak trimming. Age at debeaking has no effect. The observations are inconclusive concerning the possibility of heightened nociception.

Cell death organizes the postnatal development of the trigeminal innervation of the cerebral vasculature.

In the adult trigeminal ganglion single cell bodies that innervate the middle cerebral artery (MCA) are different from but situated near to one or more cell bodies that innervate the forehead (O'Connor and Van der Kooy, submitted). Multiple fluorescent retrograde axonal tracing in postnatal day 3-90 rats was employed to describe the development of this adult pattern of trigeminal projections. We found that close to 90% of the cells that innervate the MCA at postnatal day 5 (PND 5) are eliminated by PND 90. Less than 20% of the ganglion cells innervating the forehead die over the same postnatal period. Subpopulations of cells in the ganglion were observed to have a maximal rate of death during different postnatal periods. First, 15-20% of the cells throughout the ophthalmic division die between PND 5 and PND 10. Second, a small population of cells that had early projections to the contralateral MCA die out completely by PND 22. Third, cells with a projection only to the MCA die primarily between PND 10 and PND 54. Fourth, during the first postnatal week there are many cells that project to both the MCA and the forehead; however, 90% of this population dies by PND 90. This elimination is observed latest in the postnatal period, with these cells exhibiting their greatest rate of cell death between PND 22 and PND 90. Thus, cell death is the primary postnatal mechanism that produces this organization in the ophthalmic division of the trigeminal ganglion and retraction of axonal collaterals is a minor mechanism. We suggest that the latest period of death in cells with divergent artery and forehead projections as well as the ultimate persistence of some artery projecting cells beyond PND 90, may be due to the larger peripheral fields of innervation of these trigeminal ganglion cells.