Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

Olga Golonzhka; Alex Nord; Paul L F Tang; Susan Lindtner; Athena R Ypsilanti; Elisabetta Ferretti; Axel Visel; Licia Selleri; John L R Rubenstein

doi:10.1016/j.neuron.2015.10.045

Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

Neuron. 2015 Dec 16;88(6):1192-1207. doi: 10.1016/j.neuron.2015.10.045. Epub 2015 Dec 6.

Authors

Olga Golonzhka¹, Alex Nord², Paul L F Tang³, Susan Lindtner⁴, Athena R Ypsilanti⁴, Elisabetta Ferretti⁵, Axel Visel⁶, Licia Selleri⁷, John L R Rubenstein⁸

Affiliations

¹ Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA; Acetylon Pharmaceuticals, 70 Fargo Street, Suite 205, Boston, MA 02210, USA. Electronic address: ogolonzhka@acetylon.com.
² Departments of Neurobiology, Physiology, and Behavior and Psychiatry and Behavioral Sciences, Center for Neuroscience, University of California Davis, Davis, CA 95618, USA.
³ Institute for Human Genetics, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
⁴ Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA.
⁵ Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA; The Danish Stem Cell Center, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
⁶ Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA; School of Natural Sciences, University of California, Merced, Merced, CA 95343, USA.
⁷ Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
⁸ Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: john.rubenstein@ucsf.edu.

Abstract

We demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2(+/-) sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Animals, Newborn
Cerebral Cortex / embryology*
Cerebral Cortex / growth & development*
Homeodomain Proteins / physiology*
Mice
Mice, Transgenic
Mitosis / physiology
Neural Stem Cells / physiology*
Neurons / physiology*
Pre-B-Cell Leukemia Transcription Factor 1
Reelin Protein
Stem Cells / physiology
Transcription Factors / physiology*

Substances

Homeodomain Proteins
Pbx1 protein, mouse
Pre-B-Cell Leukemia Transcription Factor 1
Reelin Protein
Transcription Factors
RELN protein, human
Reln protein, mouse

Associated data

GEO/GSE73288

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding