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Examining the Role of the Surfactant Family Member SFTA3 in Interneuron Specification

Christopher Y. Chen, Nickesha C. Anderson, Sandy Becker, Martin Schicht, Christopher Stoddard, Lars Bräuer, Friedrich Paulsen, Laura Grabel
doi: https://doi.org/10.1101/330621
Christopher Y. Chen
aDept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459 USA
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Nickesha C. Anderson
aDept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459 USA
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Sandy Becker
aDept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459 USA
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Martin Schicht
bInstitute of Functional and Clinical Anatomy, Friedrich Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
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Christopher Stoddard
cGenome Sciences, University of Connecticut Health, 263 Farmington Avenue, Farmington CT 06030
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Lars Bräuer
bInstitute of Functional and Clinical Anatomy, Friedrich Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
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Friedrich Paulsen
bInstitute of Functional and Clinical Anatomy, Friedrich Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
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Laura Grabel
aDept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459 USA
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Abstract

The transcription factor NKX2.1, expressed at high levels in the medial ganglionic eminence (MGE), is a master regulator of cortical interneuron progenitor development. To identify gene candidates with expression profiles similar to NKX2.1, previous transcriptome analysis of human embryonic stem cell (hESC)-derived MGE-like progenitors revealed SFTA3 as the strongest candidate. Quantitative real-time PCR analysis of hESC-derived NKX2.1-positive progenitors and transcriptome data available from the Allen Institute for Brain Science revealed comparable expression patterns for NKX2.1 and SFTA3 during interneuron differentiation in vitro and demonstrated high SFTA3 expression in the human MGE. Although SFTA3 has been well studied in the lung, the possible role of this surfactant protein in the MGE during embryonic development remains unexamined. To determine if SFTA3 plays a role in MGE specification, SFTA3-/- and NKX2.1 -/-hESC lines were generated using custom designed CRISPRs. We show that NKX2.1 KOs have a significantly diminished capacity to differentiate into MGE interneuron subtypes. SFTA3 KOs also demonstrated a somewhat reduced ability to differentiate down the MGE-like lineage, although not as severe relative to NKX2.1 deficiency. These results suggest NKX2.1 and SFTA3 are co-regulated genes, and that deletion of SFTA3 does not lead to a major change in the specification of MGE derivatives.

Footnotes

  • Christopher Y Chen: cychen{at}wesleyan.edu

  • Nickesha Anderson: ncanderson{at}wesleyan.edu

  • Sandy Becker: sbecker{at}wesleyan.edu

  • Martin Schicht: martin.schicht{at}fau.de

  • Christopher Stoddard: stoddard{at}uchc.edu

  • Lars Brauer: lars.braeuer{at}fau.de

  • Friedrich Paulsen: friedrich.paulsen{at}fau.de

  • Laura Grabel: lgrabel{at}wesleyan.edu

  • The authors declare no potential conflicts of interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 24, 2018.
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Examining the Role of the Surfactant Family Member SFTA3 in Interneuron Specification
Christopher Y. Chen, Nickesha C. Anderson, Sandy Becker, Martin Schicht, Christopher Stoddard, Lars Bräuer, Friedrich Paulsen, Laura Grabel
bioRxiv 330621; doi: https://doi.org/10.1101/330621
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Examining the Role of the Surfactant Family Member SFTA3 in Interneuron Specification
Christopher Y. Chen, Nickesha C. Anderson, Sandy Becker, Martin Schicht, Christopher Stoddard, Lars Bräuer, Friedrich Paulsen, Laura Grabel
bioRxiv 330621; doi: https://doi.org/10.1101/330621

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