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Distinct expression patterns for type II topoisomerases IIA and IIB in the early foetal human telencephalon
Author(s) -
Harkin Lauren F.,
Gerrelli Dianne,
Gold Diaz Diana C.,
Santos Chloe,
Alzu'bi Ayman,
Austin Caroline A.,
Clowry Gavin J.
Publication year - 2016
Publication title -
journal of anatomy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 118
eISSN - 1469-7580
pISSN - 0021-8782
DOI - 10.1111/joa.12416
Subject(s) - biology , pax6 , subventricular zone , mitosis , microbiology and biotechnology , proliferation marker , progenitor cell , cerebrum , cell growth , cell type , cell division , cerebral cortex , cell , transcription factor , gene , stem cell , neuroscience , central nervous system , genetics
TOP 2A and TOP 2B are type II topoisomerase enzymes that have important but distinct roles in DNA replication and RNA transcription. Recently, TOP 2B has been implicated in the transcription of long genes in particular that play crucial roles in neural development and are susceptible to mutations contributing to neurodevelopmental conditions such as autism and schizophrenia. This study maps their expression in the early foetal human telencephalon between 9 and 12 post‐conceptional weeks. TOP 2A immunoreactivity was restricted to cell nuclei of the proliferative layers of the cortex and ganglionic eminences ( GE ), including the ventricular zone and subventricular zone ( SVZ ) closely matching expression of the proliferation marker KI 67. Comparison with sections immunolabelled for NKX 2.1, a medial GE (MGE) marker, and PAX 6, a cortical progenitor cell and lateral GE (LGE) marker, revealed that TOP 2A‐expressing cells were more abundant in MGE than the LGE. In the cortex, TOP 2B is expressed in cell nuclei in both proliferative ( SVZ ) and post‐mitotic compartments (intermediate zone and cortical plate) as revealed by comparison with immunostaining for PAX 6 and the post‐mitotic neuron marker TBR 1. However, co‐expression with KI 67 was rare. In the GE , TOP 2B was also expressed by proliferative and post‐mitotic compartments. In situ hybridisation studies confirmed these patterns of expression, except that TOP 2A mRNA is restricted to cells in the G2/M phase of division. Thus, during early development, TOP 2A is likely to have a role in cell proliferation, whereas TOP 2B is expressed in post‐mitotic cells and may be important in controlling expression of long genes even at this early stage.