Spatiotemporal Distribution of <i>PAX6</i> and <i>MEIS2</i> Expression and Total Cell Numbers in the Ganglionic Eminence in the Early Developing Human Forebrain

Abstract

The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in nuclei of radial glia cells in the neocortical proliferative zones and controls the differentiation and neurogenetic fate of these cells in the dorsal telencephalon in rodents. Animal studies on the Meis2 gene have revealed expression in the developing telencephalon and Meis2 is known to regulate the expression of Pax6 in the eye and pancreas. Because of this functional relation between Pax6 and Meis2, we studied the spatial and temporal expression of PAX6, and MEIS2 using a developmental series of human fetal brains at 7–19 postconceptional weeks with emphasis on the forebrain to investigate whether the two genes are expressed in the same regions and zones in the same time window. We demonstrate by in situ hybridization and immunohistochemistry that the two homeobox genes are expressed during early fetal brain development in humans. PAX6 mRNA and protein were located in the proliferative zones of the neocortex and in single cells in the cortical preplate at 7 fetal weeks and in the developing cortical plate from 8 or 9 to 19 fetal weeks. The expression of PAX6 expanded into the ganglionic eminence just prior to the stage at which a stereological estimation showed an exponential rise in total cell number in this area. The MEIS2 gene was also present in the proliferative zones of the human fetal neocortex and a higher expression of MEIS2 than PAX6 was observed in these areas at 9 fetal weeks. Further, MEIS2 was expressed at a very high level in the developing ganglionic eminence and at a more moderate level in the cortical plate.

Distinct and redundant expression and transcriptional diversity of MEIS gene paralogs during chicken development

“…Meis1 was reported to be expressed in the caudal ganglionic eminence in mouse (Toresson et al, 2000), but XMeis1 is absent in the Xenopus forebrain (Maeda et al, 2002). Similar to our observation in chicken, striatal and pallial Meis2 expression was observed in the developing mouse (Toresson et al, 1999(Toresson et al, , 2000, monkey (Takahashi et al, 2008), and human forebrain (Larsen et al, 2010), and was described as possibly ''basal ventral telencephalon expression'' in zebrafish (Zerucha and Prince, 2001;Biemar et al, 2001). This partial evidence about conserved expression patterns, added to the postulated retinoid signals necessary to obtain striatal and ventral pallial Meis2-related derivatives in chicken, and to the evidence of Meis2 as a potential upstream modulator of mouse Dlx genes, suggests an early role for Meis genes in the complex telencephalic patterning process (Marklund et al, 2004;Ghanem et al, 2008).…”

“…In the chicken midbrain, expression of Meis1/2 was confirmed (Ferran et al, 2007, Agoston andBobak et al, 2009;Coy and Borycki, 2010), as also observed in Xenopus (Maeda et al, 2001(Maeda et al, , 2002, zebrafish (Biemar et al, 2001;Waskiewicz et al, 2001;Zerucha and Prince, 2001), mouse (Cecconi et al, 1997;Oulad-Abdelghani et al, 1997;Shim et al, 2007), and human (Larsen et al, 2010). Our isoform analysis by RT-PCR showed that Meis2A.1 is slightly more expressed in the chicken during development and postnatal stages.…”

TG-interacting factor 1 acts as a transcriptional repressor of sterol O-acyltransferase 2

“…Meis2 maps to human chromosome 15 ( 36 ), but, except for its involvement in developmental processes and cancer (37)(38)(39), not much is known about the function of this transcription factor. Although our transfection experiments revealed that Meis2d acts as a positive regulator of both the hepatic and intestinal SOAT2 expression ( Fig.…”

Evaluation of conserved and ultra‐conserved non‐genic sequences in chromosome 15q15‐linked periodic catatonia

“…MEIS2 was present in the proliferative zones of the human fetal neocortex and in the developing ganglionic eminence and at a more moderate level in the cortical plate [Larsen et al, 2010]. In a recent genome-wide pharmacogenomic study of metabolic side effects to antipsychotic drugs the top finding in 738 schizophrenia patients was at the MEIS2 locus, where intronic SNP rs1568679 mediated the effects of risperidone on hip and waist circumference [Adkins et al, 2011].…”