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Radial and tangential neuronal migration pathways in the human fetal brain: anatomically distinct patterns of diffusion MRI coherence - PubMed

  • ️Tue Jan 01 2013

Radial and tangential neuronal migration pathways in the human fetal brain: anatomically distinct patterns of diffusion MRI coherence

James Kolasinski et al. Neuroimage. 2013.

Abstract

Corticogenesis is underpinned by a complex process of subcortical neuroproliferation, followed by highly orchestrated cellular migration. A greater appreciation of the processes involved in human fetal corticogenesis is vital to gaining an understanding of how developmental disturbances originating in gestation could establish a variety of complex neuropathology manifesting in childhood, or even in adult life. Magnetic resonance imaging modalities offer a unique insight into anatomical structure, and increasingly infer information regarding underlying microstructure in the human brain. In this study we applied a combination of high-resolution structural and diffusion-weighted magnetic resonance imaging to a unique cohort of three post-mortem fetal brain specimens, aged between 19 and 22 post-conceptual weeks. Specifically, we sought to assess patterns of diffusion coherence associated with subcortical neuroproliferative structures: the pallial ventricular/subventricular zone and subpallial ganglionic eminence. Two distinct three-dimensional patterns of diffusion coherence were evident: a clear radial pattern originating in ventricular/subventricular zone, and a tangentio-radial patterns originating in ganglionic eminence. These patterns appeared to regress in a caudo-rostral and lateral-ventral to medial-dorsal direction across the short period of fetal development under study. Our findings demonstrate for the first time distinct patterns of diffusion coherence associated with known anatomical proliferative structures. The radial pattern associated with dorsopallial ventricular/subventricular zone and the tangentio-radial pattern associated with subpallial ganglionic eminence are consistent with reports of radial-glial mediated neuronal migration pathways identified during human corticogenesis, supported by our prior studies of comparative fetal diffusion MRI and histology. The ability to assess such pathways in the fetal brain using MR imaging offers a unique insight into three-dimensional trajectories beyond those visualized using traditional histological techniques. Our results suggest that ex-vivo fetal MRI is a potentially useful modality in understanding normal human development and various disease processes whose etiology may originate in aberrant fetal neuronal migration.

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Figures

Figure 1
Figure 1. Radial and tangential routes of GABA-ergic and glutamatergic neuronal migration in the human fetal brain

Simplified two-dimensional schematic representations of the pallial and subpallial origins and migratory routes of two major classes of cortical neurons. Glutamatergic neurons originate in the pallial ventricular zone/subventricular zone (blue), with some tangential migration within the SVZ/VZ, but a dominant pattern of radial migration along radial glial fascicles in a plane perpendicular to the orientation of the cortical plate (radial pathways: blue arrows). GABA-ergic neurons in the human brain originate from both pallial ventricular zone/subventricular zone (blue) and subpallial ganglionic eminence (green). GABA-ergic neurons from ganglionic eminence display a pattern of migration initially tangential to the orientation of the cortical surface, before assuming a radial trajectory in intermediate zone towards the cortical plate (tangential pathway: dark green arrows); a pattern reported in more diverse mammalian systems. A pattern of GABAergic neuronal migration originating in SVZ/VZ and displaying a radial trajectory to cortical plate has been reported more recently in humans and non-human primates (light green arrows). GABA-ergic neurons originating from ganglionic eminence also migrate via subcortical paths to thalamus. Migratory pathways are displayed on a schematic slice of frontal cortex from a human fetus at 19 post-conceptual weeks. GE: ganglionic eminence; VZ: ventricular zone; SVZ: subventricular zone; IZ: intermediate zone; SP: subplate; CP: cortical plate.

Figure 2
Figure 2. Overview of magnetic resonance imaging data acquired from post-mortem, formalin-fixed human fetal brain samples

Structural data were acquired for each sample using a multi-echo flash sequence with images acquired at α=40° providing optimal contrast to identify cortical and subcortical structures of interest (A-C). Diffusion-weighted MRI were acquired for each sample using a steady state free precession sequence (b= 730s/mm2; 44 directions), yielding maps of fractional anisotropy (D-F). A diffusion tensor imaging streamline tracking algorithm was used to undertake whole-brain deterministic tractography (G-I: represents visualization of tractography output data applying a coronal slice filter). RGB directional key for tractography data (bottom left): R- right, A- anterior, S- superior. Scale bar (pink): 10mm. pcw: post-conceptual weeks.

Figure 3
Figure 3. Structural MRI overview of the anatomical structures of interest: subpallial ganglionic eminence and dorsopallial ventricular zone

Structural sequences acquired at α=40° provide optimal contrast to define anatomical structures of interest. Ganglionic eminence (blue) was masked in its entirety, from hippocampus, in an arc along the lateral border of the lateral ventricle (A-C) to the anterior extremity of the anterior horn of the lateral ventricle (D). The anatomical masks of ganglionic eminence used in further analysis excluded the extension of the rostral migratory stream (E). Dorsopallial ventricular zone/subventricular zone (pink) was masked caudally from the level of the posterior extremity of ganglionic eminence and rostrally to the anterior extremity of the anterior horn of the lateral ventricle (A-D, F). The occipital and temporal components of VZ/SVZ are not easily demarcated anatomically, and were excluded from this study, which focused principally on frontal lobe development. VZ: ventricular zone; SVZ: subventricular zone.

Figure 4
Figure 4. Pattern of radial diffusion coherence in pathways originating from dorsopallial ventricular zone/subventricular zone

Tractography pathways originating in anatomically defined dorsopallial ventricular zone (Example Ai: blue) at 19, 21 and 22 pcw. A clear pattern of radial diffusion coherence is observed in pathways with a cortical trajectory, running through intermediate zone and subplate in a plane perpendicular to the orientation of the cortical surface (A, D, G). This pattern is visible along the length of the VZ/SVZ structure (C, F, I). Deviations from patterns of strictly radial diffusion coherence are observed. Within the structure of VZ/SVZ, a pattern of diffusion coherence is observed in parallel to the border of lateral ventricle (a, b, d) in the coronal plane. At 19 pcw this tangential coherence was observed in the coronal plane (a), whereas at 21 and 22 pcw, a clear pattern of diffusion coherence is visible within the VZ/SVZ in the sagittal plane (b, d) where pathways initially follow a trajectory along the A-P axis of the ventricular zone, before a clear transition to a radial coherence pattern with a cortical trajectory (c, e). A further deviation from strictly radial patterns of diffusion coherence associated with VZ/SVZ is observed in the intermediate zone at 22 pcw. Diffusion pathways originating initially in VZ/SVZ follow a radial cortical trajectory (f: red), before assuming a tangential pattern in the A-P axis through the intermediate zone (g: green), and then revert back to a radial coherence pattern before coursing into subplate and cortical plate (h: red). RGB directional key for tractography data (bottom left): R- right, A- anterior, S- superior. pcw: post-conceptual weeks.

Figure 5
Figure 5. Pattern of tangential diffusion coherence in pathways originating from subpallial ganglionic eminence

Tractography pathways originating in anatomically defined subpallial ganglionic eminence (Fig. 2E) at 19, 21 and 22 pcw. A clear pattern of diffusion coherence was apparent within the structure of the ganglionic eminence (a, b, c), with pathways following the arc of the structure along the wall of the lateral ventricles in all three samples under study. At all ages, pathways with a radial cortical trajectory were observed emanating from the ganglionic eminence (d, e, f); closer inspection demonstrated that the tangential pathways within the ganglionic eminence were continuous with these radial pathways, with a clear tangentio-radial transition in the overall trajectory (g, h, j). The emanating radial pathways showed variation in cortical trajectory across the age range studied. At 19 pcw radial pathways followed a lateral and inferior trajectory towards cortical plate (Bi/ii: red), which shifted more medially at 21 pcw (Ei/ii), and showed a clear mediodorsal dominance at 22 pcw (Hi/ii). Furthermore, the radial pathways showed a differing distribution along the caudo-rostral axis of the ganglionic eminence in the three brain samples under study. At 19 pcw, an even distribution of radial pathways was observed along the rostro-caudal axis of the GE (g) which showed a gradual shift regression caudally at 21 pcw (e) and a clear shift to rostral dominance at 22 pcw (f). These diffusion characteristics demonstrate a tangentio-radial pattern of diffusion coherence between the ganglionic eminence and cortical plate. RGB directional key for tractography data (bottom left): R- right, A- anterior, S- superior. pcw: post-conceptual weeks.

Figure 6
Figure 6. Overview of observed three-dimensional patterns in diffusion coherence associated with ganglionic eminence and dorsopallial ventricular/subventricular zone

The dorsopallial ventricular/subventricular zone and the ganglionic eminence were associated with two distinct patterns of diffusion coherence. The diffusion pathways emanating from dorsopallial ventricular zone/subventricular zone show a clear dominance in radial coherence, with individual tracts predominantly assuming a pathway directly towards cortical plate. Some deviated from the strictly radial pattern were observed in the intermediate zone, where there was a deviation from a radial to tangential trajectory in the rostrocaudal axis, before a return to a radial pathway towards cortical plate (A). Within dorsopallial ventricular zone/subventricular zone itself, diffusion coherence was tangential to the cortical surface in both the sagittal and coronal views (A/B: red lines within VZ/SVZ [blue]). Diffusion coherence within ganglionic eminence (green) showed a strong directionality tangential to the cortical surface (C), with individual streamlines showing a sharply punctuated transition upon exiting the ganglionic eminence, assuming a radial pathway coursing towards cortical plate (C/D). Both patterns of diffusion coherence demonstrated a pattern of temporal regression with a caudo-rostral (A, C) and lateral-inferior to medial dorsal (D) predominance, as described previously.

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