Mechanisms of Tangential Migration

Tangential migration, defined as a nonradial mode of migration, includes distinct types of cell movement that differ in the type of substrate used by migrating cells. Regardless of the substrate employed, tangentially migrating cells share an important common feature: they do not respect regional forebrain boundaries. Thus, cell populations engaged in tangential migration normally move over long distances and follow complex trajectories before reaching their final destination. These migrations usually involve multiple changes in the direction of the movement, which depend on changes in the environment and/or the responses of migrating neurons. In the past few years, many studies have demonstrated the existence of environmental cues that can act as contact or diffusible attractants or repellents that provide directional information to tangentially migrating neurons through interactions with cell-surface receptors (see Table 1). Here, the cellular and molecular mechanisms controlling tangential migration are reviewed using as examples two well-characterized tangential migratory populations, cortical inter-neurons and facial branchiomotor neurons.

1.11.5.1 Migration of Cortical Interneurons

The tangential migration of cortical interneurons to the cortex is, most likely, one of the most intensively studied cell populations of the developing brain since the seminal discovery of their subpallial origin in mammals (Anderson et al., 1997). Since then, several other studies have shown that a subpallial origin of cortical interneurons is a common feature to, at least, tetrapod vertebrates (Cobos et al., 2001; Gonzalez et al., 2002; Brox et al., 2003), suggesting that this is a highly conserved trait in cortical evolution.

Cells migrating tangentially to the cortex have multiple origins within the subpallium (reviewed in Corbin et al., 2001; Marin and Rubenstein, 2001), although most GABAergic interneurons seem to derive from the medial ganglionic eminence (MGE). Interestingly, the MGE is also the source of interneurons for other forebrain structures, such as the striatum (Marin et al., 2000; Wichterle et al., 2001). Consequently, most of our knowledge on the mechanisms controlling the migration of cortical interneurons refers to MGE-derived cells and it is likely that different molecules may control the migration of interneurons generated in other sub-pallial structures, such as the caudal ganglionic eminence (Nery et al., 2002).

There are several key decision points affecting the migration MGE-derived cortical interneurons. First, interneurons initiate their migration in response to factors that stimulate their movement. Second, interneurons refrain from migrating in ventral and ventromedial regions - thus avoiding the preoptic area and the septum - directing instead their movement in a dorsal direction. Third, cortical interneurons actively avoid entering the developing striatum, a target for other classes of MGE-derived interneurons. Early during development, interneurons

Table 1 Guidance factors and neuronal migration in the CNS

Gene

Function

Neuronal population

Refs.

BDNF, NT4

Growth factor; motogenic; promotes

Cortical interneurons, cortical projection neurons

a

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