Anatomical location of mature GnRH neurons corresponds with their birthdate in the developing mouse

The gonadotropin-releasing hormone (GnRH) neurons exhibit substantial functional, anatomical, and molecular heterogeneity, which has hampered their thorough examination. This study was undertaken in an effort to understand whether the anatomical distribution of GnRH neurons is related to their developmental history, because such an association may help explain differences within the population. Using bromodeoxyuridine pulse labeling of timed pregnant female mice we labeled dividing cells, including GnRH neuron progenitors in the olfactory placode, throughout the window of GnRH neuron differentiation. Our results indicate that cells that become postmitotic early tend to populate the rostral aspects of the adult GnRH neuron continuum, whereas later-generated cells tend to settle more caudally; an inside-out pattern reminiscent of neocortex. These observations suggest that the timing of differentiation influences the ability of postmitotic GnRH neurons to navigate to their adult location, and hence may be important in determining the ultimate wiring of the adult network.