Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons.

Abstract

The use of [3Hlthymidine labeling in combination with various axonal transport tracers has revealed that a subset of migrating neurons in the fetal monkey cerebrum issue axons to the opposite cerebral hemisphere while still migrating to their final positions in the cortical plate. Other cortical neurons with the same "birthdate" (i.e., that underwent their last round of DNA synthesis on the same day) are not retrogradely labeled by tracer injections of the opposite hemisphere. These findings suggest that the cardinal distinction between projection and local circuit neurons may be specified in postmitotic neurons before they acquire their fmal positions in the cortex.The layer-specific distribution of different classes of projection and local circuit neurons is a striking feature of neocortical organization (e.g., refs. 1-3 paraformaldehyde/1.25% glutaraldehyde (HRP-injected fetuses). Frozen sections of the frontal lobes were mounted on glass slides. Sections from HRP-injected brains were incubated with substrate as described (11). Both HRP and fluorescent dye sections were examined on a Lietz Orthoplan microscope equipped with appropriate fluorescent filters and attached to a computer-assisted x-y plotter.[3H]Thymidine Autoradiography. To determine the time of origin for layer III neurons of the prefrontal cortex, nine timed-pregnant female monkeys were injected with [methyl-3H]thymidine at selected gestational ages and their offspring were sacrificed postnatally (Table 1). Each animal was sacrificed by vascular perfusion with a mixed aldehyde fixative and processed for autoradiography (12,13). In addition, a series offour fetuses were injected between E70 and E77 and sacrificed at short intervals ranging between 7 and 28 days to follow the migration of prospective layer III neurons across the cerebral wall. Autoradiograms were examined with darkfield illumination to locate all labeled cells. Individual cells were classified as heavily labeled if the number of silver grains over the nucleus was greater than 50%6 ofthe maximum grain count observed in a given specimen ( Fig. 1; Abbreviations: En, embryonic day n; Pn, postnatal day n; FB, fast blue; DY, diamidino yellow; RLM, rhodamine-labeled latex microspheres; HRP, horseradish peroxidase. 1354The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Translocation of Synaptically Connected Interneurons across the Dentate Gyrus of the Early Postnatal Rat Hippocampus

“…For example, pyramidal neurons in the developing primate hippocampus occasionally display initial signs of differentiation before reaching their final destination, as indicated by the presence of basally positioned axon-like processes (Nowakowski and Rakic, 1979). Likewise, prospective callosal neurons extend axons to the opposite hemisphere while migrating to the superficial layer of the neocortex (Schwartz et al, 1991). However, in the present study, most of the migrating cells demonstrated ultrastructurally well developed input and output synapses.…”

Actomyosin Contraction at the Cell Rear Drives Nuclear Translocation in Migrating Cortical Interneurons

“…An important difference between glial-guided and non-glial-guided neuronal migration resides in the fate of the trailing process during cell movement. Radially migrating pyramidal cells leave behind long trailing processes that transform into axons (Schwartz et al, 1991;Hatanaka and Murakami, 2002). Likewise, during their radial migration cerebellar granule cells leave behind a bifurcated trailing process that will became the characteristic axon (Rakic, 1971).…”

New insights into the molecular mechanisms specifying neuronal polarity in vivo

“…Pioneering work by Pasko Rakic using Golgi staining and electron microscope (EM) serial-reconstruction of the morphology of migrating cortical neurons in primates revealed that axons emerge from their trailing process as they translocate [17]. This was confirmed by retrograde axon tracing showing that in primates, the cell bodies of a substantial number of callosal pyramidal neurons already have an axon in the contra-lateral hemisphere as their cell body translocates radially [18].…”