Two specific populations of GABAergic neurons originating from the medial and the caudal ganglionic eminences aid in proper navigation of callosal axons

Abstract

The corpus callosum (CC) plays a crucial role in interhemispheric communication. It has been shown that CC formation relies on the guidepost cells located in the midline region that include glutamatergic and GABAergic neurons as well as glial cells. However, the origin of these guidepost GABAergic neurons and their precise function in callosal axon pathfinding remain to be investigated. Here, we show that two distinct GABAergic neuronal subpopulations converge toward the midline prior to the arrival of callosal axons. Using in vivo and ex vivo fate mapping we show that CC GABAergic neurons originate in the caudal and medial ganglionic eminences (CGE and MGE) but not in the lateral ganglionic eminence (LGE). Time lapse imaging on organotypic slices and in vivo analyses further revealed that CC GABAergic neurons contribute to the normal navigation of callosal axons. The use of Nkx2.1 knockout (KO) mice confirmed a role of these neurons in the maintenance of proper behavior of callosal axons while growing through the CC. Indeed, using in vitro transplantation assays, we demonstrated that both MGE- and CGE-derived GABAergic neurons exert an attractive activity on callosal axons. Furthermore, by combining a sensitive RT-PCR technique with in situ hybridization, we demonstrate that CC neurons express multiple short and long range guidance cues. This study strongly suggests that MGE- and CGE-derived interneurons may guide CC axons by multiple guidance mechanisms and signaling pathways.

Commissural axonal corridors instruct neuronal migration in the mouse spinal cord

“…Our data support a role for commissural axons in neurophilic migration and, to the best of our knowledge, provide the first experimental evidence that commissural axonal fascicles act as border landmarks delimiting neuronal migration named 'axon-restricted migration'. Several studies have shown that conversely, appropriate clustering of cell bodies can influence the axon to be guided appropriately [7][8][9] . Furthermore, it is well established that both axons and neuronal cell bodies are influenced by direct chemotactic mechanisms 5 .…”

“…As axons and neuronal cell bodies from different populations are guided simultaneously during development and are in close apposition, it seems plausible that forming axonal fascicles and cell bodies physically influence each other's behaviour. A small number of studies have shown that the position of cell bodies influence the guidance of axons by the production of chemotactic cues [7][8][9] . Conversely, there is also evidence to support the idea that pioneer axons provide a growth substrate for newly migrating axons and cell bodies [10][11][12] .…”

Quiescent neuronal progenitors are activated in the juvenile guinea pig lateral striatum and give rise to transient neurons

“…Rather, transient neurons have been described during embryonic development and early postnatal stages (Niquille et al, 2009;Teissier et al, 2012) and, at least in the neocortex, it has been suggested that their death is regulated by intrinsically defined mechanisms (Southwell et al, 2012). Interestingly, these cells are often directed to white matter tracts, where they contribute to the guidance of growing axons (López-Bendito et al, 2006;Niquille et al, 2009Niquille et al, , 2013Sato et al, 1998). Moreover, these cells originate, in part, from the caudal ganglionic eminence, a major source of Sp8 + interneurons (Ma et al, 2012;Niquille et al, 2013).…”

“…Interestingly, these cells are often directed to white matter tracts, where they contribute to the guidance of growing axons (López-Bendito et al, 2006;Niquille et al, 2009Niquille et al, , 2013Sato et al, 1998). Moreover, these cells originate, in part, from the caudal ganglionic eminence, a major source of Sp8 + interneurons (Ma et al, 2012;Niquille et al, 2013). These observations raise the possibility that the transient EC-LS neuroblasts belong to a broader population of cells involved in transient forms of plasticity, possibly related to the remodeling of long-range connections.…”

Contralateral targeting of the corpus callosum

“…Sources of these guidance cues include populations of guidepost cells (of both glial and neuronal identity) situated at various stages along the callosal tract. Examples of such populations are the indusium griseum at the midline dorsal border of the corpus callosum (Shu and Richards, 2001), the glial wedge ventral to the corpus callosum and medial to the lateral ventricles (Shu and Richards, 2001;Shu et al, 2003c), and the midline corridor, which lies ventral and dorsal to the corpus callosum at the midline (Silver et al, 1982;Shu et al, 2003b;Niquille et al, 2009;Niquille et al, 2013).…”