Serotonergic Neurons Migrate Radially through the Neuroepithelium by Dynamin-Mediated Somal Translocation

Abstract

Embryonic CNS neurons can migrate from the ventricular zone to their final destination by radial glial-guided locomotion. Another less appreciated mechanism is somal translocation, where the young neuron maintains its primitive ventricular and pial processes, through which the cell body moves. A major problem in studying translocation has been the identification of neuronal-specific markers that appear in primitive, radially shaped cells. We used enhanced yellow fluorescent protein under control of the Pet-1 enhancer/promoter region (ePet-EYFP), a specific marker of early differentiated serotonergic neurons, to study their migration via immunohistology and time-lapse imaging of living slice cultures. As early as E10.0, ePet-EYFP-expressing neurons were axonless, radially oriented, and spanned the entire neuroepithelium. The soma translocated within the pial process toward the pial surface and could also translocate through its neurites, which sprouted from the pial process. The dynamin inhibitor dynasore significantly reduced translocation velocity, while the nonmuscle myosin II inhibitor blebbistatin and the kinesin inhibitor AMP-PNP had no significant effect. Here we show for the first time that serotonergic neurons migrate by somal translocation mediated, in part, by dynamin.

Leading Tip Drives Soma Translocation via Forward F-Actin Flow during Neuronal Migration

“…A recent study of the radial migration of embryonic serotonergic neurons in a slice culture preparation showed that soma translocation of these neurons was independent of myosin II, but depended on the microtubule-based motor protein dynamin (Hawthorne et al, 2010). It is likely that the proper migration of neurons in developing brain may involve the complementary and/or redundant function of multiple motor proteins (Bellion et al, 2005).…”

Serotonin: a regulator of neuronal morphology and circuitry

“…[16]) and within the first gestational month in primates [17]. Serotonergic neurons migrate to and position themselves within the raphe nuclei from the ventricular zone via somal translocation rather than radial-glial guided migration [18]. Subsequent outgrowth and innervation is highly regulated.…”

“…Engineered transgenes and fluorescent reporters under control of the serotonin-specific Pet-1 enhancer region are available in mice [94] and zebrafish [95] and this technique has allowed the investigation of developmental serotonergic neuronal migration in slice culture [18] and development of the 5-HT 1A conditional knockout that is selectively targeted to serotonergic neurons [62]. In rats, viral vectors have been delivered to central serotonergic neurons in vivo and in slice culture, allowing expression of fluorescent reporters and visualization of serotonergic projections [96,97].…”

Functional Interplay between Dopaminergic and Serotonergic Neuronal Systems during Development and Adulthood

“…5-HT is first detected at E10.5 in the mouse. 66 The onset of 5-HT genes depends on several transcription factors, such as Pet1, which is the only known transcription factor present exclusively in 5-HT neurons, and Lmx1b, which is expressed more broadly in the developing brain and is also crucial for the development of mDA neurons. 67–73 …”

“…66 This movement of 5-HT neurons occurs sequentially according to their date of birth: The oldest, and hence earliest, migrating neurons will be the first to reach and remain closest to the pial surface. Later born neurons migrate after the older neurons, and thus ultimately reside in a position more distant from the pial surface.…”