Apparently, olfactory axons and GnRH producing neurons are among the first neurons that migrate from neural crest at around 39th day of gestation in humans (Cassoni et al., 2016).
In rodents, early GnRH neurons migrate together with a heterogeneous
coalescence of placode-derived and neural crest-derived migratory
cells (Forni et al., 2011) and olfactory axons, collectively called
the ‘migratory mass’ (MM) (Miller et al., 2010; Valverde et al.,
1992). This cell migration precedes the targeting of olfactory sensory
axons to the developing olfactory bulb (OB). The existence of a
similar MM in the human embryo has not yet been described. We thus
immunolabeled consecutive sagittal sections of a CS 16 embryo† for GnRH
and doublecortin (DCX) (Fig. 1D,E,G), a marker of immature migratory
neurons (Gleeson et al., 1999). We identified a very small number (50
in total) of immature GnRH-expressing cells in the nasal mesenchyme,
in the medial portion of the olfactory placode (Fig. 1C-E), adjacent
to the basal lamina of the VNO, showing that the acquisition of cell
identity occurs outside the VNO between GW 5 and 6. At this stage, we
observed a mixed mass of immature GnRH neurons expressing DCX (Fig.
1F,G) or βIII-tubulin (Fig. 1H-J), migrating across the nasal
mesenchyme towards the telencephalon. As in rodents (Miller et al.,
2010), GnRH neurons in humans only represented a small proportion of
the MM (Fig. 1G). Furthermore, these pioneer neurons of the MM
expressed the delta/notch-like EGF repeat containing (DNER) (Fig.
1H-J), a transmembrane protein specifically localized in the dendrites
and cell bodies of postmitotic neurons.
†Carnegie stage (CS) 16 = ∼39th day of gestation