Abstract
The mammalian main olfactory bulb (OB) has a large population of GABAergic inhibitory interneurons that contains several subtypes defined by the co-expression other neurotransmitters and calcium binding proteins. The three most commonly studied OB interneuron subtypes co-express either Calretinin, Calbindin, or Tyrosine hydroxylase (Th). Combinations of transcription factors used to specify the phenotype of progenitors are referred to as transcription factor codes, and the current understanding of transcription factor codes that specify OB inhibitory neuron phenotypes are largely based on studies in mice. The conservation of these transcription factor codes in the human OB, however, has not been investigated. The aim of this study was to establish whether transcription factor codes in OB interneurons are conserved between mice and humans. This study compared the co-expression of Foxp2, Meis2, Pax6, and Sp8 transcription factors with Calretinin, Calbindin, or Th in human and mouse OB interneurons. This analysis found strong conservation of Calretinin co-expression with Sp8 and Meis2 as well as Th co-expression with Pax6 and Meis2. This analysis also showed that selective Foxp2 co-expression with Calbindin was conserved between mice and humans, which suggests Foxp2 is a novel determinant of the OB Calbindin interneuron phenotype. Together, the findings in this study provide insight into the conservation of transcription codes for OB interneuron phenotypes between humans and mice, as well as reveal some important differences between the species. This advance in our understanding of transcription factor codes in OB interneurons provides an important complement to the codes that have been established for other regions within the mammalian central nervous system, such as the cortex and spinal cord.
Highlights
Neural circuit development requires the assembly of many neurons with distinct phenotypes
We examined a select group of transcription factors to establish whether their co-expression with Calretinin, Calbindin, or Tyrosine hydroxylase has been conserved between mice and humans
For the olfactory bulb (OB) dopaminergic phenotype, strong co-expression with Pax6 was conserved between mice and humans
Summary
Neural circuit development requires the assembly of many neurons with distinct phenotypes. Molecular mechanisms that direct neuronal progenitor differentiation are critical for providing the phenotypic diversity necessary for circuit development. Neuronal differentiation is marked by the expression of transcription factors that divide neural progenitor domains into distinct territories. OB Interneuron Transcription Factor Codes and subdivides these territories into regions that produce progenitors for a subset of phenotypes. In the OB glomerular layer, odorant information is relayed from olfactory sensory neuron axons to mitral/tufted cells. The transmission of odorant information from mitral/tufted cells to other cortical regions is regulated by inhibitory neurons in the granule cell layer. Most OB inhibitory neurons are GABAergic, but there are many sub-types that are defined by the differential coexpression of other neurotransmitters, neuroactive peptides, and calcium binding proteins (Kosaka et al, 1998; Panzanelli et al, 2007; Parrish-Aungst et al, 2007). The three most commonly studied interneuron phenotypes are defined by the expression of either Calretinin or Calbindin calcium binding proteins, or Tyrosine hydroxylase (Th; the rate-limiting enzyme for dopamine biosynthesis)
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