Reelin expression during embryonic development of the pig brain

Abstract

BackgroundReelin is an extracellular glycoprotein of crucial importance in the developmental organisation of neurons in the mammalian cerebral cortex and other laminated brain regions. The pig possesses a gyrencephalic brain that bears resemblance to the human brain. In order to establish an animal model for neuronal migration disorders in the pig, we have studied the expression pattern and structure of Reelin during pig brain development.ResultsWe determined the sequence of pig Reelin mRNA and protein and identified a high degree of homology to human Reelin. A peak in Reelin mRNA and protein expression is present during the period of major neurogenesis and neuronal migration. This resembles observations for human brain development. Immunohistochemical analysis showed the highest expression of Reelin in the Cajal-Reztius cells of the marginal zone, in resemblance with observations for the developing brain in humans and other mammalian species.ConclusionsWe conclude that the pig might serve as an alternative animal model to study Reelin functions and that manipulation of the pig Reelin could allow the establishment of an animal model for human neuronal migration disorders.

Controversies in RELN/reelin expression in otosclerosis

“…VII., n. VIII. and n. IX.-Jacobson's nerve) and several neuroectodermal elements (membranous labyrinth, organ of Corti, spiral ganglion), which are neccessary to be escorted by reelin during the early phase of embryonic development [19]. It should be noted that the stapes footplate is an essential part of the otic capsule by the embryonic point of view [1].…”

“…It should be noted that the stapes footplate is an essential part of the otic capsule by the embryonic point of view [1]. At the later stages of embryonic development, RELN mRNA expression may not be required, since synaptic formation and neural integration process are laid oV within the otic capsule [1,19]. Furtheromore, post-embryonic bone remodeling is totally absent in the otic capsule in order to prevent the biomechanical aspects of the organ of Corti [1].…”

“…Expression of reelin has been reported to be signiWcantly decreased in bipolar disorder and in schizophrenia; however, these observations remain unclear as several studies showed that psychotropic medication itself aVects the RELN mRNA expression [22,25]. With regard to our current knowledge, reelin is expressed exclusively by neural tissues (ganglia, brain, and cerebellum) and no signiWcant expression has been found in other non-neural tissue specimens [19,20,22]. Reelin is also expressed by odontoblasts, which are premature cells at the anatomical borders of dental pulp [27].…”

“…The association between the SNPs (single nucleotide polymorphism) of RELN gene and otosclerosis appears as the most interesting genetic observation, since the protein, reelin, is exclusively expressed by neural tissues [18][19][20]. The RELN gene is located to the chromosome 7q22.1 and contains 64 active exons [21].…”

“…RELN encodes an extreme large and excreted extracellular matrix protein named as reelin [21,22]. Reelin is considered to be a special decoy receptor that regulates the primary neuronal and neuroglial interactions, which are critical steps for cell positioning and also for Wnal neuronal migration during human brain development [19,21,22]. Reelin has a serine-protease activity that is important for the modulation of cell adhesion [22].…”