Adhesion molecule Amigo2 is involved in the fasciculation process of the fasciculus retroflexus

Abstract

Background The fasciculus retroflexus is the prominent efferent pathway from the habenular complex. Medial habenular axons form a core packet whereas lateral habenular axons course in a surrounding shell. Both groups of fibers share the same initial pathway but differ in the final segment of the tract, supposedly regulated by surface molecules. The gene Amigo2 codes for a membrane adhesion molecule with an immunoglobulin‐like domain 2 and is selectively expressed in the medial habenula. We present it as a candidate for controlling the fasciculation behavior of medial habenula axons. Results First, we studied the development of the habenular efferents in an Amigo2 lack of function mouse model. The fasciculus retroflexus showed a variable defasciculation phenotype. Gain of function experiments allowed us to generate a more condensed tract and rescued the Amigo2 knock‐out phenotype. Changes in Amigo2 function did not alter the course of habenular fibers. Conclusion We have demonstrated that Amigo2 plays a subtle role in the fasciculation of the fasciculus retroflexus.

Atypical Course of the Habenulo‐Interpeduncular Tract in Chick Embryos

“…2021; Company et al. 2022). The constant paramedian position of the ulterior tegmental course of the retroflex tract across pretectum and midbrain possibly bespeaks of a subtle attraction by the local floorplate neighborhood or local radial glia (which we have seen also express BEN; Figure 6c–f), or alternatively, an adhesive fasciculation with some other contingent of descending longitudinal basal fibers (though nothing specific about this possibility is known so far).…”

“…2021; Company et al. 2022). It seems possible to ascribe tentatively some causal roles to different navigational conditions the fibers appear to find at each locus.…”

“…The causal determinants of these four different behaviors manifested in series by supposedly similar though essentially somewhat heterogeneous fibers (due to separate origins in distinct and by no means homogeneous medial and lateral habenular nuclei) remain largely unknown, though some recent progress has accrued (e.g., Company, Moreno-Cerdá et al 2021;Company et al 2022). It seems possible to ascribe tentatively some causal roles to different navigational conditions the fibers appear to find at each locus.…”

“…Why they retroflect caudalwards and essentially do not turn rostralwards remains an obscure point (though mice devoid of some gene functions do produce rostrally coursing retroflex tract fibers at this locus, Moreno-Bravo et al 2016). There is perhaps a gradient of attracting signals increasing across the midbrain tegmentum into the hindbrain that orients the fibers caudalwards, or the retroflexion decision is helped by some repellent signal placed rostrally in the diencephalic tegmentum, or both (see recent experimental data on retroflex tract guidance by Moreno-Bravo et al 2016 andCompany, Moreno-Cerdá et al 2021;Company et al 2022). The constant paramedian position of the ulterior tegmental course of the retroflex tract across pretectum and midbrain possibly bespeaks of a subtle attraction by the local floorplate neighborhood or local radial glia (which we have seen also express BEN; Figure 6c-f), or alternatively, an adhesive fasciculation with some other contingent of descending longitudinal basal fibers (though nothing specific about this possibility is known so far).…”