A novel floor plate boundary defined by adjacent En1 and Dbx1 microdomains distinguishes midbrain dopamine and hypothalamic neurons

Development. 2017 Mar 1;144(5):916-927. doi: 10.1242/dev.144949. Epub 2017 Feb 7.

Abstract

The mesodiencephalic floor plate (mdFP) is the source of diverse neuron types. Yet, how this structure is compartmentalized has not been clearly elucidated. Here, we identify a novel boundary subdividing the mdFP into two microdomains, defined by engrailed 1 (En1) and developing brain homeobox 1 (Dbx1). Utilizing simultaneous dual and intersectional fate mapping, we demonstrate that this boundary is precisely formed with minimal overlap between En1 and Dbx1 microdomains, unlike many other boundaries. We show that the En1 microdomain gives rise to dopaminergic (DA) neurons, whereas the Dbx1 microdomain gives rise to subthalamic (STN), premammillary (PM) and posterior hypothalamic (PH) populations. To determine whether En1 is sufficient to induce DA neuron production beyond its normal limit, we generated a mouse strain that expresses En1 in the Dbx1 microdomain. In mutants, we observed ectopic production of DA neurons derived from the Dbx1 microdomain, at the expense of STN and PM populations. Our findings provide new insights into subdivisions in the mdFP, and will impact current strategies for the conversion of stem cells into DA neurons.

Keywords: Boundary; Dopamine; Fate map; Floor plate; Mouse; Premammillary; Subthalamic.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Dopaminergic Neurons / cytology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / metabolism*
  • Hypothalamus / embryology*
  • Male
  • Mesencephalon / embryology*
  • Mice
  • Mice, Transgenic
  • Neurons / cytology*
  • Signal Transduction
  • Stem Cells / metabolism

Substances

  • Dbx1 protein, mouse
  • En1 protein, mouse
  • Homeodomain Proteins