Tfap2a and 2b act downstream of Ptf1a to promote amacrine cell differentiation during retinogenesis

Kangxin Jin, Haisong Jiang, Dongchang Xiao, Min Zou, Jun Zhu, Mengqing Xiang

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Retinogenesis is a precisely controlled developmental process during which different types of neurons and glial cells are generated under the influence of intrinsic and extrinsic factors. Three transcription factors, Foxn4, RORβ1 and their downstream effector Ptf1a, have been shown to be indispensable intrinsic regulators for the differentiation of amacrine and horizontal cells. At present, however, it is unclear how Ptf1a specifies these two cell fates from competent retinal precursors. Here, through combined bioinformatic, molecular and genetic approaches in mouse retinas, we identify the Tfap2a and Tfap2b transcription factors as two major downstream effectors of Ptf1a. RNA-seq and immunolabeling analyses show that the expression of Tfap2a and 2b transcripts and proteins is dramatically downregulated in the Ptf1a null mutant retina. Their overexpression is capable of promoting the differentiation of glycinergic and GABAergic amacrine cells at the expense of photoreceptors much as misexpressed Ptf1a is, whereas their simultaneous knockdown has the opposite effect. Given the demonstrated requirement for Tfap2a and 2b in horizontal cell differentiation, our study thus defines a Foxn4/RORβ1-Ptf1a-Tfap2a/2b transcriptional regulatory cascade that underlies the competence, specification and differentiation of amacrine and horizontal cells during retinal development.

Original languageEnglish
Article number8
JournalMolecular Brain
Volume8
Issue number1
DOIs
StatePublished - 13 May 2015
Externally publishedYes

Keywords

  • Amacrine cell
  • Foxn4
  • Horizontal cell
  • Ptf1a
  • Retinal development
  • Tfap2

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