Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex

Eva Helga Rosenthal

Research output: Book/anthology/thesis/reportPh.D. thesisResearch

Abstract

Combinatorial expression of sets of transcription factors (TFs) along the mammalian cortex controls its subdivision into functional areas. Unlike neocortex, only few recent data suggest genetic mechanisms controlling the regionalization of the archicortex.

TF Emx2 plays a crucial role in patterning of the cortex. In this work, from a preselection of 10 genes from previously performed microarray screen, at least six genes were identified to reveal altered expression in Emx2 deficiency, placing them as putative players acting downstream of Emx2 in cortical arealization.

Secondly, findings from performed functional analysis of the generated knockout mutant mice for TF Zbtb20 are presented, implicating that this factor, while being dispensable for prenatal development, exerts a genetic control for arealization of archicortex. The expression of Zbtb20 in cortical germinal neuroepithelium begins at E12.5, while later on becoming restricted exclusively to postmitotic neurons of hippocampus (Hi) proper, dentate gyrus (DG), and two transitory zones, subiculum (S) and retrosplenial cortex (Rsp). Analysis of Zbtb20-/- mice revealed altered cortical patterning at the border between neocortex and archicortex, a misspecification of the retrosplenial (neocortical) domain, decreased size of archicortical derivatives (S, Hi proper, DG), and a dramatic change in the molecular patterning of the hippocampal fields S, CA1, CA2, CA3. Dorsally located fields were ectopically expanded into their neighboring, more ventral fields. As Zbtb20 was observed to be expressed only after the accomplishment of early progenitor specification, the intrinsic area specification of cortical progenitors appeared unaltered.
A second phenotype is the observed marked delay of the ossification in the Zbtb20-/- mutant mice. In Zbtb20 deficiency, the detected defect in growth of hippocampus and DG as well as in skeletal ossification most probably involves modulation of Wnt signaling.
In conclusion, the presented results in this work place Zbtb20 as the first known so far TF with a role in postmitotic acquisition of areal identity of the archicortex and its subfields.
Original languageEnglish
Place of PublicationUniversity of Braunschweig, Germany
Number of pages151
Publication statusPublished - 2. Jun 2010

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Neocortex
Osteogenesis
Workplace
Neurons
Growth

Keywords

  • Zbtb20, Hippocampus, Corticogenesis, Neurodevelopmental Biology, Emx2

Cite this

Rosenthal, E. H. (2010). Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex. University of Braunschweig, Germany.
Rosenthal, Eva Helga. / Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex. University of Braunschweig, Germany, 2010. 151 p.
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abstract = "Combinatorial expression of sets of transcription factors (TFs) along the mammalian cortex controls its subdivision into functional areas. Unlike neocortex, only few recent data suggest genetic mechanisms controlling the regionalization of the archicortex.TF Emx2 plays a crucial role in patterning of the cortex. In this work, from a preselection of 10 genes from previously performed microarray screen, at least six genes were identified to reveal altered expression in Emx2 deficiency, placing them as putative players acting downstream of Emx2 in cortical arealization.Secondly, findings from performed functional analysis of the generated knockout mutant mice for TF Zbtb20 are presented, implicating that this factor, while being dispensable for prenatal development, exerts a genetic control for arealization of archicortex. The expression of Zbtb20 in cortical germinal neuroepithelium begins at E12.5, while later on becoming restricted exclusively to postmitotic neurons of hippocampus (Hi) proper, dentate gyrus (DG), and two transitory zones, subiculum (S) and retrosplenial cortex (Rsp). Analysis of Zbtb20-/- mice revealed altered cortical patterning at the border between neocortex and archicortex, a misspecification of the retrosplenial (neocortical) domain, decreased size of archicortical derivatives (S, Hi proper, DG), and a dramatic change in the molecular patterning of the hippocampal fields S, CA1, CA2, CA3. Dorsally located fields were ectopically expanded into their neighboring, more ventral fields. As Zbtb20 was observed to be expressed only after the accomplishment of early progenitor specification, the intrinsic area specification of cortical progenitors appeared unaltered.A second phenotype is the observed marked delay of the ossification in the Zbtb20-/- mutant mice. In Zbtb20 deficiency, the detected defect in growth of hippocampus and DG as well as in skeletal ossification most probably involves modulation of Wnt signaling.In conclusion, the presented results in this work place Zbtb20 as the first known so far TF with a role in postmitotic acquisition of areal identity of the archicortex and its subfields.",
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Rosenthal, EH 2010, Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex. University of Braunschweig, Germany.

Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex. / Rosenthal, Eva Helga.

University of Braunschweig, Germany, 2010. 151 p.

Research output: Book/anthology/thesis/reportPh.D. thesisResearch

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T1 - Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex

AU - Rosenthal, Eva Helga

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N2 - Combinatorial expression of sets of transcription factors (TFs) along the mammalian cortex controls its subdivision into functional areas. Unlike neocortex, only few recent data suggest genetic mechanisms controlling the regionalization of the archicortex.TF Emx2 plays a crucial role in patterning of the cortex. In this work, from a preselection of 10 genes from previously performed microarray screen, at least six genes were identified to reveal altered expression in Emx2 deficiency, placing them as putative players acting downstream of Emx2 in cortical arealization.Secondly, findings from performed functional analysis of the generated knockout mutant mice for TF Zbtb20 are presented, implicating that this factor, while being dispensable for prenatal development, exerts a genetic control for arealization of archicortex. The expression of Zbtb20 in cortical germinal neuroepithelium begins at E12.5, while later on becoming restricted exclusively to postmitotic neurons of hippocampus (Hi) proper, dentate gyrus (DG), and two transitory zones, subiculum (S) and retrosplenial cortex (Rsp). Analysis of Zbtb20-/- mice revealed altered cortical patterning at the border between neocortex and archicortex, a misspecification of the retrosplenial (neocortical) domain, decreased size of archicortical derivatives (S, Hi proper, DG), and a dramatic change in the molecular patterning of the hippocampal fields S, CA1, CA2, CA3. Dorsally located fields were ectopically expanded into their neighboring, more ventral fields. As Zbtb20 was observed to be expressed only after the accomplishment of early progenitor specification, the intrinsic area specification of cortical progenitors appeared unaltered.A second phenotype is the observed marked delay of the ossification in the Zbtb20-/- mutant mice. In Zbtb20 deficiency, the detected defect in growth of hippocampus and DG as well as in skeletal ossification most probably involves modulation of Wnt signaling.In conclusion, the presented results in this work place Zbtb20 as the first known so far TF with a role in postmitotic acquisition of areal identity of the archicortex and its subfields.

AB - Combinatorial expression of sets of transcription factors (TFs) along the mammalian cortex controls its subdivision into functional areas. Unlike neocortex, only few recent data suggest genetic mechanisms controlling the regionalization of the archicortex.TF Emx2 plays a crucial role in patterning of the cortex. In this work, from a preselection of 10 genes from previously performed microarray screen, at least six genes were identified to reveal altered expression in Emx2 deficiency, placing them as putative players acting downstream of Emx2 in cortical arealization.Secondly, findings from performed functional analysis of the generated knockout mutant mice for TF Zbtb20 are presented, implicating that this factor, while being dispensable for prenatal development, exerts a genetic control for arealization of archicortex. The expression of Zbtb20 in cortical germinal neuroepithelium begins at E12.5, while later on becoming restricted exclusively to postmitotic neurons of hippocampus (Hi) proper, dentate gyrus (DG), and two transitory zones, subiculum (S) and retrosplenial cortex (Rsp). Analysis of Zbtb20-/- mice revealed altered cortical patterning at the border between neocortex and archicortex, a misspecification of the retrosplenial (neocortical) domain, decreased size of archicortical derivatives (S, Hi proper, DG), and a dramatic change in the molecular patterning of the hippocampal fields S, CA1, CA2, CA3. Dorsally located fields were ectopically expanded into their neighboring, more ventral fields. As Zbtb20 was observed to be expressed only after the accomplishment of early progenitor specification, the intrinsic area specification of cortical progenitors appeared unaltered.A second phenotype is the observed marked delay of the ossification in the Zbtb20-/- mutant mice. In Zbtb20 deficiency, the detected defect in growth of hippocampus and DG as well as in skeletal ossification most probably involves modulation of Wnt signaling.In conclusion, the presented results in this work place Zbtb20 as the first known so far TF with a role in postmitotic acquisition of areal identity of the archicortex and its subfields.

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M3 - Ph.D. thesis

BT - Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex

CY - University of Braunschweig, Germany

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Rosenthal EH. Transcription Factor Zbtb20 Controls Regional Specification of Mammalian Archicortex. University of Braunschweig, Germany, 2010. 151 p.