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Review
. 2019 Apr 30;10:982.
doi: 10.3389/fpsyg.2019.00982. eCollection 2019.

Building an Asymmetrical Brain: The Molecular Perspective

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Free PMC article
Review

Building an Asymmetrical Brain: The Molecular Perspective

Judith Schmitz et al. Front Psychol. .
Free PMC article

Abstract

The brain is one of the most prominent examples for structural and functional differences between the left and right half of the body. For handedness and language lateralization, the most widely investigated behavioral phenotypes, only a small fraction of phenotypic variance has been explained by molecular genetic studies. Due to environmental factors presumably also playing a role in their ontogenesis and based on first molecular evidence, it has been suggested that functional hemispheric asymmetries are partly under epigenetic control. This review article aims to elucidate the molecular factors underlying hemispheric asymmetries and their association with inner organ asymmetries. While we previously suggested that epigenetic mechanisms might partly account for the missing heritability of handedness, this article extends this idea by suggesting possible alternatives for transgenerational transmission of epigenetic states that do not require germ line epigenetic transmission. This is in line with a multifactorial model of hemispheric asymmetries, integrating genetic, environmental, and epigenetic influencing factors in their ontogenesis.

Keywords: Nodal pathway; epigenetics; handedness; language lateralization; laterality.

Figures

Figure 1
Figure 1
The major types of body plans. (A) Asymmetry. (B) Radial symmetry. (C) Bilateral symmetry. (D) Due to the asymmetrical position of internal organs, humans and other vertebrates have been described as pseudo-bilateral (Levin, 2005).
Figure 2
Figure 2
The time course of asymmetry development. (A) Visceral asymmetries. (B) Structural hemispheric asymmetries. (C) Motor asymmetries. (D) Language lateralization.
Figure 3
Figure 3
The development of visceral asymmetries. Motile cilia (red) induce a leftward nodal flow, which is transduced into stronger left-sided Ca2+ signaling and Nodal expression, triggering the Nodal signaling pathway in the left lateral plate mesoderm (LPM).
Figure 4
Figure 4
The Nodal signaling cascade. Facilitated by Gdf1, Nodal is transmitted to the left LPM, expressing Nodal, Lefty2, and Pitx2. The protein encoded by Lefty2 suppresses the Nodal pathway in the right LPM. Pitx2 encodes a transcription factor that is involved in asymmetric morphogenesis.
Figure 5
Figure 5
Alternative forms of transgenerational epigenetic inheritance. (A) Germ line epigenetic inheritance: An environmental factor acts on the F0 generation and induces an epigenetic state that is transmitted to subsequent, unaffected individuals via the germ line. (B) Experience-dependent epigenetic inheritance: Maternal behavior induces an epigenetic state in the offspring (F1) that in turn influences F1 behavior toward its offspring (F2) transmitting behavior and epigenetic states across generations. (C) Gene-dependent epigenetic inheritance: A genetic factor modulates the probability of an environmental factor that influences F1 epigenetic states. As F1 likely transmits the genetic factor to F2, epigenetic states are transmitted across generations.
Figure 6
Figure 6
Epigenetic reprogramming. Reprogramming occurs shortly after fertilization in the zygote and in the primordial germ cells of the developing embryo. At both stages, some epigenetic states are able to escape reprogramming.
Figure 7
Figure 7
Experience-dependent epigenetic inheritance. Independent of licking and grooming behavior (LG) of the biological mother, the experience of high LG is associated with a large number of ERα receptors and high LG behavior, while the experience of low LG behavior is associated with a low number of ERα receptors and low LG behavior.

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References

    1. Abu-Rustum R. S., Ziade M. F., Abu-Rustum S. E. (2013). Reference values for the right and left fetal choroid plexus at 11 to 13 weeks: an early sign of “developmental” laterality? J. Ultrasound Med. 32, 1623–1629. 10.7863/ultra.32.9.1623, PMID: - DOI - PubMed
    1. Albrechtsen S., Rasmussen S., Dalaker K., Irgens L. M. (1998). Reproductive career after breech presentation: subsequent pregnancy rates, interpregnancy interval, and recurrence. Obstet. Gynecol. 92, 345–350. 10.1016/S0029-7844(98)00176-8, PMID: - DOI - PubMed
    1. Alqadah A., Hsieh Y.-W., Morrissey Z. D., Chuang C.-F. (2018). Asymmetric development of the nervous system. Dev. Dyn. 247, 124–137. 10.1002/dvdy.24595, PMID: - DOI - PMC - PubMed
    1. Ambeskovic M., Roseboom T. J., Metz G. A. S. (2017a). Transgenerational effects of early environmental insults on aging and disease incidence. Neurosci. Biobehav. Rev. 10.1016/j.neubiorev.2017.08.002 (in press). - DOI - PubMed
    1. Ambeskovic M., Soltanpour N., Falkenberg E. A., Zucchi F. C. R., Kolb B., Metz G. A. S. (2017b). Ancestral exposure to stress generates new behavioral traits and a functional hemispheric dominance shift. Cereb. Cortex 27, 2126–2138. 10.1093/cercor/bhw063. - DOI - PMC - PubMed

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