A novel floor plate boundary defined by adjacent En1 and Dbx1 microdomains distinguishes midbrain dopamine and hypothalamic neurons.
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 betweenEn1andDbx1microdomains, unlike many other boundaries. We show that theEn1microdomain gives rise to dopaminergic (DA) neurons, whereas theDbx1microdomain 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 theDbx1microdomain. In mutants, we observed ectopic production of DA neurons derived from theDbx1microdomain, 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.
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Navid
N
Nouri
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA r-awatramani@northwestern.edu.
Rajeshwar
0000-0002-0713-2140
R
Awatramani
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D059290:Dopaminergic Neurons / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D007031:Hypothalamus / Q000196:embryology*; D008297:Male; D008636:Mesencephalon / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism
C103403:Dbx1 protein, mouse; C080330:En1 protein, mouse; D018398:Homeodomain Proteins
Boundary; Dopamine; Fate map; Floor plate; Mouse; Premammillary; Subthalamic