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MCPH1: a window into brain development and evolution.

Pulvers JN, Journiac N, Arai Y, Nardelli J - Front Cell Neurosci (2015)

Bottom Line: Many factors influence the development of the cerebral cortex to its normal size and neuronal composition.MCPH1 causes microcephaly in mice and humans and is involved in a diverse array of molecular functions beyond brain development, including DNA repair and chromosome condensation.In this review, we will present an overview of MCPH1 from these multiple angles, and whilst its specific role in brain size regulation during development and evolution remain elusive, the pieces of the puzzle will be discussed with the aim of putting together the full picture of this fascinating gene.

View Article: PubMed Central - PubMed

Affiliation: Sydney Medical Program, University of Sydney Sydney, Australia.

ABSTRACT
The development of the mammalian cerebral cortex involves a series of mechanisms: from patterning, progenitor cell proliferation and differentiation, to neuronal migration. Many factors influence the development of the cerebral cortex to its normal size and neuronal composition. Of these, the mechanisms that influence the proliferation and differentiation of neural progenitor cells are of particular interest, as they may have the greatest consequence on brain size, not only during development but also in evolution. In this context, causative genes of human autosomal recessive primary microcephaly, such as ASPM and MCPH1, are attractive candidates, as many of them show positive selection during primate evolution. MCPH1 causes microcephaly in mice and humans and is involved in a diverse array of molecular functions beyond brain development, including DNA repair and chromosome condensation. Positive selection of MCPH1 in the primate lineage has led to much insight and discussion of its role in brain size evolution. In this review, we will present an overview of MCPH1 from these multiple angles, and whilst its specific role in brain size regulation during development and evolution remain elusive, the pieces of the puzzle will be discussed with the aim of putting together the full picture of this fascinating gene.

No MeSH data available.


Related in: MedlinePlus

ClustalX alignment of human MCPH1 and mouse Mcph1 proteins. Conserved amino acids are shown in bold characters. Blue upper lines indicate BRCT domains, and red underlines indicate nuclear localization signals (Gavvovidis et al., 2012). Amino acid residues mutated in microcephaly (either nonsense or missense; see Table 1; Figure 1) are in red.
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Figure 2: ClustalX alignment of human MCPH1 and mouse Mcph1 proteins. Conserved amino acids are shown in bold characters. Blue upper lines indicate BRCT domains, and red underlines indicate nuclear localization signals (Gavvovidis et al., 2012). Amino acid residues mutated in microcephaly (either nonsense or missense; see Table 1; Figure 1) are in red.

Mentions: In human and mouse (Mus musculus), the MCPH1 coding sequence contains 14 exons, distributed across 200 kb of genomic DNA. The protein contains three BRCT (BRCA1 C-Terminal) domains (Figures 1, 2), which were first described in BRCA proteins and mediate protein-protein interactions (Koonin et al., 1996; Huyton et al., 2000). One domain is located at the N-terminal side of the MCPH1 protein (BRCT1), and a tandem of two domains spans the C-terminal sequence (BRCT2/3). These domains are predicted to be crucial for function (Jeffers et al., 2008) and may be differentially involved in the diverse roles of MCPH1 by mediating interactions with distinct partners. In line with this notion, repeats of BRCT domains, such as BRCT2/3, have been shown to preferentially interact with phosphorylated residues (Woods et al., 2012).


MCPH1: a window into brain development and evolution.

Pulvers JN, Journiac N, Arai Y, Nardelli J - Front Cell Neurosci (2015)

ClustalX alignment of human MCPH1 and mouse Mcph1 proteins. Conserved amino acids are shown in bold characters. Blue upper lines indicate BRCT domains, and red underlines indicate nuclear localization signals (Gavvovidis et al., 2012). Amino acid residues mutated in microcephaly (either nonsense or missense; see Table 1; Figure 1) are in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376118&req=5

Figure 2: ClustalX alignment of human MCPH1 and mouse Mcph1 proteins. Conserved amino acids are shown in bold characters. Blue upper lines indicate BRCT domains, and red underlines indicate nuclear localization signals (Gavvovidis et al., 2012). Amino acid residues mutated in microcephaly (either nonsense or missense; see Table 1; Figure 1) are in red.
Mentions: In human and mouse (Mus musculus), the MCPH1 coding sequence contains 14 exons, distributed across 200 kb of genomic DNA. The protein contains three BRCT (BRCA1 C-Terminal) domains (Figures 1, 2), which were first described in BRCA proteins and mediate protein-protein interactions (Koonin et al., 1996; Huyton et al., 2000). One domain is located at the N-terminal side of the MCPH1 protein (BRCT1), and a tandem of two domains spans the C-terminal sequence (BRCT2/3). These domains are predicted to be crucial for function (Jeffers et al., 2008) and may be differentially involved in the diverse roles of MCPH1 by mediating interactions with distinct partners. In line with this notion, repeats of BRCT domains, such as BRCT2/3, have been shown to preferentially interact with phosphorylated residues (Woods et al., 2012).

Bottom Line: Many factors influence the development of the cerebral cortex to its normal size and neuronal composition.MCPH1 causes microcephaly in mice and humans and is involved in a diverse array of molecular functions beyond brain development, including DNA repair and chromosome condensation.In this review, we will present an overview of MCPH1 from these multiple angles, and whilst its specific role in brain size regulation during development and evolution remain elusive, the pieces of the puzzle will be discussed with the aim of putting together the full picture of this fascinating gene.

View Article: PubMed Central - PubMed

Affiliation: Sydney Medical Program, University of Sydney Sydney, Australia.

ABSTRACT
The development of the mammalian cerebral cortex involves a series of mechanisms: from patterning, progenitor cell proliferation and differentiation, to neuronal migration. Many factors influence the development of the cerebral cortex to its normal size and neuronal composition. Of these, the mechanisms that influence the proliferation and differentiation of neural progenitor cells are of particular interest, as they may have the greatest consequence on brain size, not only during development but also in evolution. In this context, causative genes of human autosomal recessive primary microcephaly, such as ASPM and MCPH1, are attractive candidates, as many of them show positive selection during primate evolution. MCPH1 causes microcephaly in mice and humans and is involved in a diverse array of molecular functions beyond brain development, including DNA repair and chromosome condensation. Positive selection of MCPH1 in the primate lineage has led to much insight and discussion of its role in brain size evolution. In this review, we will present an overview of MCPH1 from these multiple angles, and whilst its specific role in brain size regulation during development and evolution remain elusive, the pieces of the puzzle will be discussed with the aim of putting together the full picture of this fascinating gene.

No MeSH data available.


Related in: MedlinePlus