Transient maternal hypothyroxinemia at onset of corticogenesis alters tangential migration of medial ganglionic eminence‐derived neurons

Abstract

Correct positioning of cortical neurons during development depends on the radial migration of the projection neurons and on the coordinated tangential and radial migrations of the subcortically generated interneurons. As previously shown, a transient and moderate maternal deficiency in thyroxin during early corticogenesis alters the radial migration of projection neurons. To determine if a similar effect might also affect tangential migration of medial ganglionic eminence (MGE)-derived neurons at the origin of cortical interneurons, explants of MGE from green fluorescent protein (GFP)-transgenic embryos were implanted into flat cortical mounts from wild-type embryos. The distances covered and the preferential migration (medially) of GFP-MGE neurons from embryos of hypothyroxinemic dams are not affected in their tangential migration into wild-type control cortices. In contrast, when GFP-MGE neurons from embryos of control or hypothyroxinemic dams migrate within cortices from embryos of hypothyroxinemic dams, the GFP-MGE-derived neurons lose their preferential direction of migration, although they still migrate for long distances throughout the cortex. Our results show that maternal hypothyroxinemia alters the tangential migration of GFP-MGE-derived neurons in the neocortex of the progeny and suggest that this alteration is not derived from the migratory neurons themselves but through undefined short- and long-range cues responsible for the guidance of their migration.

Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

“…in Zoeller and Rovet, 2004;Bernal, 2005;Bernal, 2007;Williams, 2008). The events controlled by THs comprise cellular proliferation, migration, and neuronal and glial cell differentiation (Narayanan and Narayanan, 1985;Berbel et al, 1993;Berbel et al, 1994;Lucio et al, 1997;Auso et al, 2004;Cuevas et al, 2005). Clinical and experimental studies have demonstrated that THs are essential for normal brain development.…”

“…These deficits depend on specific cellular impairments. Indeed, during the prenatal period, THs influence neurogenesis, neuronal proliferation and migration in the cerebral cortex, hippocampus and medial ganglionic eminence (Narayanan and Narayanan, 1985;Lucio et al, 1997;Auso et al, 2004;Cuevas et al, 2005). Axonal outgrowth, dendritic branching and synaptogenesis, together with the initiation of glial cell differentiation and migration are also affected by TH deficiency at prenatal stages (Portfield and Hendrich, 1993;Morreale de Escobar et al, 2000;Bernal et al, 2003).…”

Do children with congenital hypothyroidism exhibit abnormal cortical morphology?

“…When TH is missing, fundamental neurobiological processes such as neurogenesis, neuronal migration, synaptogenesis, and myelination develop atypically (7), while structures such as hippocampus (8), striatum (9), and cortex (10,11) are abnormal. Within the cortex, a late gestational/early postnatal TH insufficiency is associated with disturbed corticogenesis due to abnormal asymmetric division of neurons migrating toward the cortical surface (12).…”

Iodine deficiency during pregnancy: a national cross-sectional survey in Latvia

“…These substantial consequences result from the fact that even mild iodine deficiency disrupts the metabolism of thyroid hormones, which are a critical endocrine regulator of early brain development (9) . Thyroid hormones act specifically by regulating the genes that underlie major neurodevelopmental events, including neurogenesis, axon and dendrite formation, neuronal migration, synaptogenesis and myelination (10)(11)(12)(13)(14) . Thyroid hormones are also involved in the regulation of BMR and macronutrient metabolism (15) .…”