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The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development.

ABSTRACT: The Olf-1/EBF helix-loop-helix (HLH) transcription factor has been implicated in olfactory gene regulation and in B-cell development. Using homology screening methods, we identified two additional Olf-1/EBF-like cDNAs from a mouse embryonic cDNA library. The Olf-1/EBF-like (O/E) proteins O/E-1, O/E-2, and O/E-3 define a family of transcription factors that share structural similarities and biochemical activities. Although these O/E genes are expressed within olfactory epithelium in an identical pattern, they exhibit different patterns of expression in the developing nervous system. Although O/E-1 mRNA is present in several tissues in addition to olfactory neurons and developing B-cells, O/E-2 and O/E-3 are expressed at high levels only in olfactory tissue. In O/E-1 knock-out animals, the presence of two additional O/E family members in olfactory neurons may provide redundancy and allow normal olfactory neurodevelopment. Further, the identification of the O/E family of HLH transcription factors and their embryonic expression patterns suggest that the O/E proteins may have a more general function in neuronal development.

SUBMITTER: Wang SS

PROVIDER: S-EPMC6573563 | biostudies-literature | 1997 Jun

REPOSITORIES: biostudies-literature

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The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development.

Wang S S SS Tsai R Y RY Reed R R RR

The Journal of neuroscience : the official journal of the Society for Neuroscience 19970601 11

The Olf-1/EBF helix-loop-helix (HLH) transcription factor has been implicated in olfactory gene regulation and in B-cell development. Using homology screening methods, we identified two additional Olf-1/EBF-like cDNAs from a mouse embryonic cDNA library. The Olf-1/EBF-like (O/E) proteins O/E-1, O/E-2, and O/E-3 define a family of transcription factors that share structural similarities and biochemical activities. Although these O/E genes are expressed within olfactory epithelium in an identical ...[more]

PMID: 9151732

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Project description:BackgroundMammalian motor circuits display remarkable cellular diversity with hundreds of motor neuron (MN) subtypes innervating hundreds of different muscles. Extensive research on limb muscle-innervating MNs has begun to elucidate the genetic programs that control animal locomotion. In striking contrast, the molecular mechanisms underlying the development of axial muscle-innervating MNs, which control breathing and spinal alignment, are poorly studied.MethodsOur previous studies indicated that the function of the Collier/Olf/Ebf (COE) family of transcription factors (TFs) in axial MN development may be conserved from nematodes to simple chordates. Here, we examine the expression pattern of all four mouse COE family members (mEbf1-mEbf4) in spinal MNs and employ genetic approaches in both nematodes and mice to investigate their function in axial MN development.ResultsWe report that mEbf1 and mEbf2 are expressed in distinct MN clusters (termed "columns") that innervate different axial muscles. Mouse Ebf1 is expressed in MNs of the hypaxial motor column (HMC), which is necessary for breathing, while mEbf2 is expressed in MNs of the medial motor column (MMC) that control spinal alignment. Our characterization of Ebf2 knock-out mice uncovered a requirement for Ebf2 in the differentiation program of a subset of MMC MNs and revealed for the first time molecular diversity within MMC neurons. Intriguingly, transgenic expression of mEbf1 or mEbf2 can rescue axial MN differentiation and locomotory defects in nematodes (Caenorhabditis elegans) lacking unc-3, the sole C. elegans ortholog of the COE family, suggesting functional conservation among mEbf1, mEbf2 and nematode UNC-3.ConclusionsThese findings support the hypothesis that genetic programs controlling axial MN development are deeply conserved across species, and further advance our understanding of such programs by revealing an essential role for Ebf2 in mouse axial MNs. Because human mutations in COE orthologs lead to neurodevelopmental disorders characterized by motor developmental delay, our findings may advance our understanding of these human conditions.

Project description:In vertebrates, pluripotent pharyngeal mesoderm progenitors produce the cardiac precursors of the second heart field as well as the branchiomeric head muscles and associated stem cells. However, the cellular and molecular mechanisms underlying the transition from multipotent progenitors to distinct heart and muscle precursors remain obscured by the complexity of vertebrate embryos. Here, using the ascidian Ciona intestinalis as a simple chordate model for cardiopharyngeal development, we show that bipotent progenitors are transcriptionally primed to activate both heart and pharyngeal muscle regulatory programs, which become restricted to the corresponding precursors following a conserved pattern of asymmetric divisions. Localized expression of COE (Collier/OLF1/EBF) then orchestrates the transition to a pharyngeal muscle fate both by promoting an MRF (Myogenic Regulatory Factor)-associated core myogenic program in myoblasts and by maintaining an undifferentiated state in their sister precursors through Notch-mediated lateral inhibition. Using single cell lineage tracing, we show that the latter are stem-like muscle precursors, which form most of the juvenile body wall muscles following proliferation, self-renewal, re-activation of MRF, and migration. We discuss the implications of our findings for the development and evolution of the cardiopharyngeal mesoderm in chordates. We combined fluorescence-activated cell sorting (FACS) and whole genome transcription profiling following perturbations of COE function to characterize the transcriptional dynamics underlying the specification of heart and ASM precursors in the ascidian cardiopharyngeal lineage. We used whole genome transcription profiling of FACS-purified cell populations isolated from 21 hpf larvae expressing FoxF>COE, FoxF>COE::WRPW or the FoxF>NLS::lacZ control. To gain insights into the transcriptional dynamics underlying fate specification in the cardiopharyngeal lineage, we also purified B7.5-lineage cells from control embryos and larvae collected every two hours from 8 to 28 hpf. This time window encompasses all developmental transitions from early TVC specification till ASM ring formation and initial differentiation.

Dataset Information

The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development.

Publications

The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development.

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