Foxn4 acts synergistically with Mash1 to specify subtype identity of V2 interneurons in the spinal cord.
Neuronal subtype diversification is essential for the establishment of functional neural circuits, and yet the molecular events underlying neuronal diversity remain largely to be defined. During spinal neurogenesis, the p2 progenitor domain, unlike others in the ventral spinal cord, gives rise to two intermingled but molecularly distinct subtypes of interneurons, termed V2a and V2b. We show here that the Foxn4 winged helix/forkhead transcription factor is coexpressed with the bHLH factor Mash1 in a subset of p2 progenitors. Loss of Foxn4 function eliminates Mash1 expression and V2b neurons and causes a fate-switch to V2a neurons, whereas the absence of Mash1 displays a similar but less severe phenotype. Overexpression of Foxn4 alone in spinal neural progenitors promotes the V2a fate at the expense of the V2b fate, whereas Mash1 suppresses both the V2a and V2b fates. However, coexpression of both Foxn4 and Mash1 promotes the V2b fate while inhibiting the V2a fate, indicating that Foxn4 cooperates with Mash1 to specify the identity of V2b neurons from bipotential p2 progenitors.
Li
Shengguo
S
Center for Advanced Biotechnology and Medicine and Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA.
Misra
Kamana
K
Matise
Michael P
MP
Xiang
Mengqing
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism* / Q000502:physiology; D001973:Bromodeoxyuridine; D002642:Chick Embryo; D017931:DNA Primers; D018274:Electroporation; D005136:Eye Proteins / Q000378:metabolism* / Q000502:physiology; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000378:metabolism* / Q000502:physiology; D005697:Galactosides; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007211:Indoles; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology*
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D017931:DNA Primers; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D005697:Galactosides; D007211:Indoles; C499317:Ascl1 protein, mouse; C438622:Foxn4 protein, mouse; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside